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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003

Bioanalytical Report Bioanalytical Report Status: Final

Bioanalytical Report Amendments Attached: None

Study Title: A placebo-controlled single-blind Phase I Study to assess the pharmacodynamics effect on glucose metabolism of three different single subcutaneous doses of DG3173 compared to octreotide and placebo in healthy male subjects.

Product Name: Octreotide and DG3173

Sponsor: Aspireo Pharmaceuticals Limited 1 Azrieli Center Tel Aviv, 67021 Israel Contact: Carsten Dehning E-mail: [email protected] Phone: (+49) 170 630 86 87

Principal Investigator: PD Dr. Manuel Haschke Clinical Pharmacology & Toxicology, University Hospital Basel Hebelstrasse 2, 4031 Basel, Switzerland Phone: (+41) 61 328 68 66 Fax: (+41) 61 265 45 60 Medical Monitor Prof. Dr. Klaus Kutz for Aspireo: AccelPharm Hebelstrasse 15A, 4056 Basel, Switzerland Phone: (+41) 61 273 55 44 Fax.: (+41) 61 273 55 48 Test Facility: Phase I Research Unit

Clinical Pharmacology & Toxicology, University Hospital Basel Hebelstrasse 2, 4031 Basel, Switzerland Phone: (+41) 61 328 68 66 Fax: (+41) 61 265 45 60

Protocol Study No: CEPHA code: CPA 430-13 Sponsor’s code: DG3173-I-003

Development Phase: Clinical Phase I

CRO/Study Director: CEPHA s.r.o. Komenského 19, CZ-323 00 Pilsen Czech Republic Contact: Dipl. Ing. Bohdan Němec E-mail: [email protected]

Phone: +420 377 540 079

Date of the Report: January 22, 2014

Compliance Status: GLP/GCP

Bioanalytical Report: CPA 430-13 Final Version / January 22, 2014

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mailto:[email protected]

mailto:[email protected]

CEPHA s.r.o. Study Code: Sponsor's Study Code:

SIGNATURE

Study No: CPA 430-13

CPA 430-13 DG3173-l-003

Study Title: A placebo-controlled single-blind Phase I Study to assess the pharmacodynamic effect on glucose metabolism of three different single subcutaneous doses of DG3 l 73 compared to octreotide and placebo in healthy male subjects

Sponsor: Aspireo Pharmaceuticals Limited 1 Azrieli Center Tel Aviv, 67021 Israel

The following report has been reviewed and the analytical activities relevant to this report were performed in compliance with Good Clinical and Laboratory Practice and/or other appropriate regulations as well as CEP HA applicable Standard Operating Procedures.

To the best oj my knowledge, this Bioanalytical Report accurately describes the study methods and procedures used, and the reported results accurately reflect the raw data.

Date Dipl. Ing. Bohdan Němec Study Director

Bioanalytical Report: CPA 430-13 Fina! Version I January 22, 2014

CEPHA s.r.o. Study Code: Sponsor's Study Code:

CEPHA Quality Assurance Unit Komenského 19, CZ-323 00 Pilsen

CPA 430-13 DG3173-l-003

QUALITY ASSURANCE STATEMENT

Report No. : Bioanalytical Report: CP A 430-13

tel: +420 377 540 079 fax: +420 377 540 432

Study Title: A placebo-controlled single-blind Phase I Study to assess pharmacodynamic effect on glucose metabolism of three different single subcutaneous doses of DG3173 compared to octreotide and placebo in healthy male subjects.

Sponsor: Aspireo Pharmaceuticals Ltd.

1 Azrieli Center Tel Aviv 67021 Israel

This Report has been reviewed and the audit oj certain phases oj the analytical activities relevant to this report were performed by the CEP HA Quality Assurance Unit in compliance with Good Laboratory and Good Clinical Practice andlor other appropriate regulations as well as CEPHA applicable Standard Ope rating Procedures.

DATEREPORTSENTTO AUDIT DATE Study Director Management

QA SPECIALIST

B ioanalytical Study September 3, 2013 September 3, 2013 January 22, 2014 Mgr. P .Třmínková Pian Analytical part September 24, 2013 September 24, 2013 J anuary 22, 2014 Mgr. P.Třmínková

Bioanalytical October 15-16, October 15-16, 2013 J anuary 22, 2014 Mgr. P. Třmínková Data 2013 B ioanalytical December 23, 2013 December 23, 2013 January 22, 2014 Mgr. P. Třmínková Report J anuary 22, 2014 J anuary 22, 2014

To the best oj my knowledge, this Bioanalytical Report has been carried aut and related activities were conducted and data were recorded and reported according to appropriate regulatory requirements (GCP/GLP), and applicable CEPHA SOP and accurately describes the methods and procedures used, and the reported results accurately reflect the raw data.

Date Dipl. Ing. Milada Balounová QA Director

Bioanalytical Report: CPA 430-13 Fina! Version I January 22, 2014



Table of Contents

Signature 2 Quality Assurance Statement 3 Table of Contents 4 Abbreviations 6 1 Summary of the Analytical Method 7 1.1 Description of Method 7 1.2 Instrumentation 7 1.3 Chromatographic Conditions 7 1.4 Detection Conditions 7 2 Description of Compounds 8 3 Calibration 9 3.1 Principles 9 3.2 Preparation of Stock and Working Calibration Standard Solution 9 3.3 Biological Calibration Standards 10 4 Quality Control Standards 10 4.1 Principles 10 4.2 Preparation of QC Stock and Working QC Standard Solution 11 4.3 Biological QC Standards 12 5 Internal Standard 12 5.1 Preparation of Stock and Working Internal Standard Solutions 12 6 Description of Samples 12 6.1 Labeling of Samples 12 6.2 Receipt of Samples 13 6.3 Transport and Storage of Samples 13 7 Analytical Runs 13 7.1 Composition of Analytical Runs 13 7.2 Summary of Analytical Runs 13 8 Evaluation of Calibration Curves 14 9 Calculation of Analyte Plasma Concentrations 15 10 Re-assay of Study Samples 17 10.1 Run Acceptance Criteria Not Met 17 10.2 Analyte Concentration above Lower Limit of Quantification (LLOQ)

in a Pre-dose Sample 17 10.3 Results Found above Upper Limit of Quantification (ULOQ) 17 10.4 Other Re-assays 17 10.5 Incurred Sample Reanalysis (ISR) 17

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11 Results 18 12 Pre-Study Validation Summary 18 13 In-Study Validation 23 13.1 Back Calculated Lower Limit of Quantification (LLOQ) 23 13.2 Precision and Accuracy 23 13.2.1 Overall Between-run Precision (CV) 23 13.2.2 Overall Between-run Accuracy (Rel. Error) 24 13.3 Calibration Curves Correlation Coefficient 24 13.4 Long-term Stability 25 14 In-Study Descriptive Statistics 25 14.1 In-Study Back Calculated Calibration Standards Summary 25 14.2 In-Study Back Calculated QC Standards Summary 26 15 Document Archiving 28 16 References 28 Tables 29 Table 1. Analytical Runs Schedule of Octreotide and DG3173 30 Table 2A. Calibration Curves Summary of Octreotide 30 Table 2B. Calibration Curves Summary of DG3173 30 Table 3A. Summary of Back-calculated Calibration Standards of Octreotide 31 Table 3B. Summary of Back-calculated Calibration Standards of DG3173 31 Table 4A. Summary of Back-calculated QC Standards of Octreotide 32 Table 4B. Summary of Back-calculated QC Standards of DG3173 32 Table 5A. Summary of Calibration Standards Accuracy of Octreotide 33 Table 5B. Summary of Calibration Standards Accuracy of DG3173 33 Table 6. Evaluated Subject Concentration Data of Octreotide and DG3173 34 Table 7. Bioassay Data 37 Appendix 1 - Copies of 100% of Chromatograms 44

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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 ABBREVIATIONS

A value acceptable AcN acetonitrile CO2 carbon dioxide CV coefficient of variation, precision DG DG3173 EC excluded from calculation g gram H2O water HCOOH formic acid I.S. internal standard K3EDTA tripotassium salt of ethylendiaminetetraacetic acid LLOQ lower limit of quantitation LC-MS/MS liquid chromatography with tandem mass spectrometry MeOH methanol mL milliliter MRM multiple reaction monitoring M/z mass to charge ratio N/A not applicable ng nanogram (NH4)2CO3 ammonium carbonate OCT octreotide QC quality control standard/sample Rel. Error, RE relative error, accuracy S calibration standard ULOQ upper limit of quantification v/v volume/volume W.I.S. working internal standard µL microliter


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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 The analysis of Octreotide and DG3173 in human plasma as well as the following report was carried out according to CEPHA SOPs based on GLP/GCP guidelines. 1 Summary of the Analytical Method The validated analytical methods SOP CPA MET 125-02 was used for Octreotide and DG3173 determination in study samples. 1.1 Description of Method Human plasma samples with octreotide, DG3173 and the internal standard were extracted on solid phase SUPELTM - SELECT HLB cartridge (Supelco). The eluent was evaporated under nitrogen to dryness and reconstituted. An aliquot of 10 µL was injected into the LC system with MS/MS detection. Octreotide and DG 3173 concentrations were quantified by the internal standard method. The samples were stored at -25°C (range -20°C to -35°C) before analysis. Sample volume 1.0 mL of plasma was needed for the assay. Octreotide and DG3173 concentrations were quantified by the internal standard method. The preparation of standards, sample processing and chromatographic conditions is thoroughly described in SOP CPA MET 125-02. 1.2 Instrumentation The samples were analyzed on LC-MS/MS system consisted of LC Waters Acquity UPLC (CPA-C-154) and MS/MS detector Waters XEVO TQ MS (CPA-M-185). The signal was recorded by software MassLynx V4.1, SCN 843 (Waters, USA). Software TargetLynx V4.1, SCN 843, module of MassLynx V4.1 (Waters, USA) was used for the data evaluation. 1.3 Chromatographic Conditions Octreotide and DG3173 chromatography was performed on reversed-phase column Atlantis T3, 10 cm x 3.0 mm, 3 µm, from Waters. Mobile phase was (AcN – 20 mM (NH4)2CO3 (85:15, v/v)) –MeOH, (95:5 v/v). The chromatographic separation was isocratically performed at 40°C at flow-rate 0.40 mL/min 1.4 Detection Conditions MS/MS detection, ES+, MRM mode DG3173: MRM of 1124 → 233 M/z Octreotide: MRM of 1020 → 120 M/z Internal Standard: MRM of 466 → 184 M/z


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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 2 Description of Compounds DG3173 Acetate - standard Molecular Formula: C58H70N12O10.C2H4O2 Molecular Weight: 1183.35 CAS No.: N/A DG3173 - analyte Molecular Formula: C58H70N12O10 Molecular Weight: 1123.3 CAS No. : N/A OCTREOTIDE Acetate - standard Molecular Formula: C49H66N10O10S2.2C2H4O2 Molecular Weight: 1139.36 CAS No : 79517-01-4

OCTREOTIDE - analyte Molecular Formula: C49H66N10O10S2 Molecular Weight: 1019.24 CAS No : 83150-76-9 Cisapride monohydrate - internal standard (±)-cis-4-amino-5-chloro-N-(1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl)-2-methoxybenzamide Molecular Formula: C23H29ClFN3O4 Molecular Weight: 465.95 CAS No. : 81098-60-4


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3. Calibration 3.1 Principles A calibration curve of DG3173 and octreotide consists of a blank, blank processed with internal standard and eight standards prepared in the same biological matrix as the study samples (human K3EDTA plasma). The calibration standards should cover the range from the pre-defined lower limit of quantification (LLOQ, S8) to the highest expected concentration (ULOQ, S1) of the analyte in the study samples. The biological calibration standards were prepared before the bioassay start and were stored at -25°C (range -20°C to -35°C) along with the study samples. The biological calibration standards were prepared in three steps in accordance with the scheme given in the SOP CPA MET 125-02:

• preparation of octreotide and DG 3173 neat standards solution in methanol-water (10:90, v/v), see chapter 3.2

• preparation of biological calibration standards S1 by spiking of blank plasma with the neat solution of calibration standards, see chapter 3.3

• preparation of biological calibration standards S2 – S8 by dilution of standard S1 by blank plasma, see chapter 3.3

3.2 Preparation of Stock and Working Calibration Standards Solutions Accurately weighed out 0.0028 g of octreotide acetate (by Sequoia Research Products), stoichiometry factor 0.8946, purity factor 0.9960, was dissolved in methanol-water (10:90, v/v) to volume 25 mL. This solution with octreotide concentration 99794.42 ng/mL, was used as STOCK OCT. Accurately weighed out 0.0026 g of DG 3173 acetate (by Bachem AG), stoichiometry factor 0.9493, purity factor 0.9604, was dissolved in methanol-water (10:90, v/v) to volume 25 mL. This solution with DG 3173 concentration 94817.60 ng/mL, was used as STOCK DG. The working neat calibration standard solution was prepared from solutions STOCK OCT and STOCK DG in accordance with the scheme:


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3.3 Biological Calibration Standards The biological calibration standards S1 – S8 were prepared by spiking of blank plasma pool by stock solution of standards and by serial dilution of the ULOQ standard by blank plasma pool in accordance with the scheme:

Octreotide and DG 3173 biological calibration standards were processed, analyzed, and evaluated for each analytical run separately (see chapter 7.1). 4 Quality Control Standards 4.1 Principles The biological quality control standards (QC) should be prepared at three – low, mid and high concentrations. Low QC should be near the LLOQ (QC3), mid QC should be in midrange of calibration curve (QC2) and high QC should be close to the ULOQ (QC1), see SOP CPA LAB 02-10: QC3 low biological quality control standards were with concentration of octreotide at

2.6 x and concentration of DG 3173 at 2.8 x of its lowest limit of quantification – LLOQ, S8.

QC2 medium biological quality control standards were with concentration of octreotide at 49.1% and concentration of DG 3173 at 50.5% of highest calibration standard – ULOQ, S1.

QC1 high biological quality control standard were with concentration of octreotide at 78.6% and concentration of DG 3173 at 80.8% of highest calibration standard – ULOQ, S1

As the calibration range of the method was found to be too wide in comparison to concentrations found in study samples one QC sample with concentration level between QC3 and QC2 was added so that two QC sample levels fall within the concentration range of study samples. This procedure is described in CEPHA SOP.

Standard Diluted Diluted Name volume Standard volume Standard

[mL] [mL]OCT DG3173

A 1.00 STOCK OCT 1.00 STOCK DG 49897.21 47408.80

Final Concentrationof Standard[ng / mL]

Standard Standard Blank PlasmaAdded Volume Added Volume Added

[ mL ] OCT DG [ mL ] OCT DG

S 1 A 0.05 49897.21 47408.80 4.95 498.97 474.09S 2 S 1 2.00 498.97 474.09 2.00 249.49 237.05S 3 S 2 1.25 249.49 237.05 2.50 83.16 79.02S 4 S 3 1.25 83.16 79.02 2.50 27.72 26.34S 5 S 4 1.25 27.72 26.34 2.50 9.24 8.78S 6 S 5 0.90 9.24 8.78 2.25 2.64 2.51S 7 S 6 0.90 2.64 2.51 2.25 0.75 0.72S 8 S 7 0.50 0.75 0.72 2.50 0.13 0.12

Concentration of standard Effective plasma conc.[ ng / mL ] [ ng / mL ]


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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 The biological quality control samples were prepared before the bioassay start but from a separate stock solution than that for the preparation of the calibration standards and were stored at -25°C (range -20°C to -35°C) along with the study samples. The biological quality control standards were prepared in three steps in accordance with the scheme given in the SOP CPA MET 125-02.

• preparation of octreotide and DG 3173 neat QC standards solution in methanol-water (10:90, v/v), see chapter 4.2

• preparation of biological quality control standard QC1 by spiking of blank plasma with the neat solution of QC standard, see chapter 4.3

• preparation of biological quality control standards QC2 and QC3 by serial dilution of QC1 by blank plasma pool, see chapter 4.3

4.2 Preparation of QC Stock and Working QC Standards Solutions Accurately weighed out 0.0022 g of octreotide acetate (by Sequoia Research Products), stoichiometry factor 0.8946, purity factor 0.9960, was dissolved in methanol-water (10:90, v/v) to volume 25 mL. This solution with octreotide concentration 78409.90 ng/mL, was used as QC STOCK OCT. Accurately weighed out 0.0021 g of DG3173 acetate (by Bachem AG), stoichiometry factor 0.9493, purity factor 0.9604, was dissolved in methanol-water (10:90, v/v) to volume 25 mL. This solution with DG3173 concentration 76583.45 ng/mL, was used as QC STOCK DG. The working neat QC standards solution was prepared from solutions QC STOCK OCT and QC STOCK DG in accordance with the scheme:

Standard Diluted Diluted Name volume Standard volume Standard OCT DG

[mL] [mL] [ng / mL] [ng / mL]

QC A 1.00 QC STOCK OCT 1.00 QC STOCK DG 39204.95 38291.72

Final Concentration


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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 4.3 Biological QC Standards The biological QC standards QC1 – QC3 were prepared by spiking of blank plasma pool by working neat solution of QC standards and serial dilution of the most concentrated QC sample QC1 by blank plasma pool in accordance with the following scheme:

Three QC samples (QC3, QC2 and QC1) in duplicate were analyzed within each run along with the study samples (see chapter 7.1) 5 Internal Standard

The internal standard was added to all biological calibration standards (S1-S8), zero sample (S0), study samples and biological quality control (QC3 – QC1) samples before the sample processing. 5.1 Preparation of Stock and Working Internal Standard Solutions Stock Internal Standard was prepared by accurate weighing out 0.0038 g of cisapride monohydrate (by Sequoia Research Products) and dissolving in MeOH-H2O (75:25, v/v) in volumetric flask to volume 50 mL accurately. This solution with cisapride concentration 76000.00 ng/mL, approx., was used as STOCK I.S. Working Internal Standard (W.I.S.) was prepared by diluting 1.0 mL of STOCK I.S. to volume 500 mL in deionized water in volumetric flask accurately. Concentration of cisapride in W.I.S. solution was 152.00 ng/mL, approx. Volume 50 µL of W.I.S. solution was added to 1.0 mL of plasma samples. 6 Description of Samples 6.1 Labeling of Samples All samples were originally labeled with the following information: • study code (DG3173-I-003) • subject number (e.g.: 1.08) • test day • sampling time • sample number • aliquot number

Standard Standard Blank PlasmaAdded Volume Added Volume

[ mL ] OCT DG [ mL ] OCT DG

QC 1 QC A 0.12 39204.95 38291.72 11.88 392.05 382.92QC 2 QC 1 4.50 392.05 382.92 2.70 245.03 239.33QC B QC 2 0.04 245.03 239.33 1.00 9.42 9.21QC 3 QC B 0.45 9.42 9.21 12.00 0.34 0.33

Concentration of standard Effective plasma conc.[ ng / mL ] [ ng / mL ]


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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 The samples were analyzed under CEPHA codes consisting of subject number – sample number. Example: Sample number RUN 01_101101 is sample 101of subject1.01. 6.2 Receipt of Samples 84 plasma samples identified as “Study No. DG3173-I-003”, (in two aliquotes), were received in polystyrene box frozen on dry ice from Phase I Research Unit, University Hospital Basel, Switzerland on July 18, 2013. 6.3 Transport and Storage of Samples The plasma samples were transported to CEPHA from Phase I Research Unit, University Hospital Basel, Switzerland in polystyrene boxes frozen on dry ice. They were delivered personally by medical monitor Prof. Dr. Klaus Kutz. The samples Study No. DG3173-I-003 were received on July 18, 2013. The delivery records of shipments are available for reference. After receipt, the samples were stored in a freezer (CPA-M-200) with controlled temperature and CO2 back-up equipment at a temperature of -25°C (range -20 to -35°C) until analysis. The temperature records of freezer are available for reference. Once the bioassay has been completed, the plasma samples were taken over by responsible person for further plasma samples storage. The temperature records of freezer will be available for reference until 15 years after study completion. 7 Analytical Runs 7.1 Composition of Analytical Runs An analytical run was processed and analyzed according to the following scheme: Blank – S0 – S8 – S7 – S6 – S5 – S4 – S3 – S2 – S1 – QC3 – study samples – QC2 – study samples – – QC1 – study samples – QC3 –study samples – QC2 – study samples – QC1, where blank blank from calibration (the same plasma as used for the calibration

standards preparation) S0 blank from calibration with internal standard added S8 – S1 calibration standards QC3 – QC1 quality control samples All plasma samples of each study animals were analyzed at random basis in one analytical run (see Table 1 and Table 7). The QC samples were evenly interspersed among all study samples in the run. 7.2 Summary of Analytical Runs Analytical run is identified as follows: RUN 01


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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 The study samples were analyzed on September 24, 2013 in the order given in Table 1 (see section Tables). 8 Evaluation of Calibration Curves The following rules were applied for calibration curve evaluation: (Excerpt from SOP CPA LAB 02-10 Calibration Curve, Quality Control Samples)

1. Number of Biological Calibration Standards A number of biological calibration standards should be adequate to anticipated calibration range and the nature of analyte/response relationship. The calibration curve should consist of 6 (six) to 8 (eight) non-zero biological standards (including LLOQ), a blank and zero sample (S0) containing internal standard only, if used.

5. Calibration Curve Acceptance Criteria A calibration curve is considered acceptable when all of the following criteria are met: 5.1 The correlation coefficient is 0.990 or better 5.2 LLOQ must be within ± 20% of the nominal value 5.3 The highest standard (ULOQ) must be within ± 10% of the nominal value 5.4 The remaining values of calibration standards must be within ± 15% of their nominal

values If standards do not meet these criteria (section 5.1-5.4) they are excluded from the regression calculation. When either ULOQ or LLOQ do not meet acceptance criteria, it is recommended to not accept the calibration curve. Under certain circumstances, the rules outlined in section 7 should be followed. 5.5 When back-calculated calibration standards, at least 75% of standards should meet

the acceptance criteria, i.e.: 5.5.1 six (6) out of seven (7) standard samples, i.e. one (1) standard sample can be

excluded from seven-non-zero-sample calibration curve 5.5.2 six (6) out of eight (8) standard samples, i.e. two (2) standard samples can be

excluded from eight-non-zero-sample calibration curve 5.6 The calibration curve is re-calculated by the same regression analysis model using

non-excluded standards. 5.7 The re-calculated calibration curve is considered acceptable if criteria 5.1-5.4 are

met. 7. Extrapolations of Calibration Curve


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7.1 Extrapolations above ULOQ and below LLOQ are not permitted. 7.2. When either ULOQ or LLOQ are excluded, the calibration curve of reduced range

may be used. Prior to authorization in writing by laboratory director is required. 7.3 Only the samples with concentrations found within the reduced concentration range

are acceptable. 7.4 When it is observed the concentrations in the study samples are in a narrower range

than originally anticipated, QC samples at additional concentrations (duplicate at each concentration) will be added to provide at least two QC sample levels falling within the range of concentrations measured in study samples.

9 Calculation of Analyte Plasma Concentrations An analytical run was considered acceptable if the standard curve and back calculated QC concentrations met the acceptance criteria laid down in CEPHA SOP (see below). (Excerpt from SOP CPA LAB 43-01 Biological Samples Analysis):

6. Analytical Run Acceptance Criteria An analytical run is considered acceptable when all of the following criteria are met:

- The system suitability test acceptance criteria are met - The calibration curve acceptance criteria are met - The QC samples acceptance criteria are met - The internal standard variability acceptance criteria are met - Blank samples of the run are free of significant interference with the analyte or

Internal Standard

6.1 System suitability test acceptance criteria

6.1.1 The CV % of analyte response in five following injects of high concentrated system suitability sample must be lower or equal to 10%.

6.1.2 The average value of the analyte response in high concentrated system

suitability sample obtained in system suitability measurements performed before and after the run containing study samples must be within ± 15%.

6.1.3 The signal of analyte in the chromatogram of the blank system suitability

sample has to be maximum 20% of the signal of analyte in the chromatogram of the LLOQ system suitability sample and the signal of internal standard in the chromatogram of the blank system suitability sample has to be maximum of 5% of the signal of internal standard in the chromatogram of the LLOQ system suitability sample.

6.1.4 Signal to noise ratio in LLOQ system suitability sample has to be at least 5.


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6.2 The calibration curve acceptance criteria are met

6.3 QC samples acceptance criteria 6.3.1 At least 4 out of 6 (or 6 out of 8) QC samples are evaluable and their

concentrations are found to be within ± 15% of the spiked concentrations.

6.3.2 When two QC concentrations at the same level are out of range, the run should be rejected.

6.4 Internal standard variability (ISV) acceptance criteria

6.4.1 Signal of internal standard in the study samples has to be in the interval ± 50% (± 80%, respectively) of the average signal of internal standard in the calibration standards.

6.4.2 If the number of the samples not meeting the ISV acceptance criteria is up to 15% of the total sample amount in the run, study director decides whether the particular samples are re-analyzed or whether the whole batch (run) is repeated.

6.4.3 The whole run has to be repeated when the amount of samples not meeting the ISV acceptance criteria is higher than 15% of the total sample amount in the run.

6.5 Blank samples of the run are free of significant interference with the analyte or Internal Standard

The evaluations of octreotide and DG3173 assays were carried out by construction of eight-point calibration graphs (excluding zero concentration) covering the range 0.13 – 498.97 ng/mL for octreotide and 0.12 – 474.09 ng/mL for DG3173. All the calibration curves coefficients were determined through weighted quadratic regression (weighing factor = 1/c2) of the octreotide / DG3173 to internal standard peak-area ratio versus octreotide / DG3173 concentration. Individual peak-area ratios of calibration standards, QCs and study samples were then substituted on the regression curve to determine values of concentration found. No manual integration was applied throughout the study bioassay, see peak Flags in Quantify Compound Summary Report. TargetLynx V4.1 peak flags abbreviations:

All processes - integrations, calibration and quantification calculations - were performed in automated mode using the software TargetLynx V4.1, SCN 843, module of MassLynx V4.1, SCN 843 (Waters).

b Peak starts or ends on the baseline.

d Peak starts or ends on a drop line. M The peak start or end point has been manually altered.

X The calibration point has been excluded from the calibration curve.

I The calibration equation could not be solved for this response. No concentration could be calculated.

- The peak has been manually deleted.


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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 Chromatograms will be available for reference until 15 years after study completion in CEPHA archive. 10 Re-Assay of Study Samples The study samples were re-assayed for the following reasons: 10.1 Run Acceptance Criteria Not Met No sample was re-analyzed for this reason, Table 1 10.2 Analyte Concentration above Lower Limit of Quantification (LLOQ) in a Pre-dose

Sample

No sample was re-analyzed for this reason, Table 1

10.3 Results Found above Upper Limit of Quantification (ULOQ) No sample was re-analyzed for this reason, Table 1 10.4 Other Re-assays No sample was re-analyzed for this reason, Table 1 10.5 Incurred Sample Reanalysis (ISR) No sample was re-analyzed for this reason according to sponsor’s requirement.


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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 11 Results All 84 received samples were assayed in CEPHA lab and results obtained during the assay of study samples are presented in Table 6 The overall bioassay results summary of bioassay run (hard copy of source data from evaluation software TargetLynx V4.1) is given in Table 7. 12 Pre-Study Validation Summary According to Appendix IV of the Guideline CHMP Guideline on the Investigation of Bioequivalence, CPMP/EWP/QWP/1401/98 Rev. 1, Presentation of Biopharmaceutical and Bioanalytical Data in Module 2.7.1, June 2012 follow the summary of pre-study validated bioanalytical method SOP CPA MET 125-02 for Octreotide and DG3173 determination in human plasma.


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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 See Appendix IV of the Guideline: Table 4.1 Bioanalytical method validation CPA MET 125-02 Octreotide Analytical Validation Report CEPHA archive This analytical method was used in the following studies: CPA 430-13 Short description of the method LC-MS/MS Biological matrix K3EDTA human plasma Analyte Octreotide Internal standard (I.S.) Cisapride monohydrate Calibration range (ng/mL) 0.13 - 498.97 Linearity (Correlation Coefficient) 0.997110 Lower limit of quantification (LLOQ) - Accuracy (%) -2.6 Lower limit of quantification (LLOQ) - Precision (%) 6.4 Standard curve concentrations (ng/mL) 0.13; 0.75; 2.64; 9.24; 27.72; 83.16; 249.49; 498.97 QC concentrations (ng/mL) 0.34; 245.03; 392.05 Between-run accuracy QC LLOQ % -4.6 Between-run accuracy QC low, mid, high % -1.8 to

3.1

Between-run precision QC LLOQ % 10.8 Between-run precision QC low, mid, high % 7.9 Within-run accuracy QC LLOQ % 7.7 Within-run accuracy QC low, mid, high % -4.4 to

5.4

Within-run precision QC LLOQ % 9.0 Within-run precision QC low, mid, high % 6.1 Matrix Factor % (Analyte low conc.) 89.9 Matrix Factor % (Analyte high conc.) 97.3 Matrix Factor % (I.S.)

96.4

CV% of IS-normalised matrix factor at low conc. 13.1 CV% of IS-normalised matrix factor at high conc. 3.3

Short term stability of working internal standard solution 6 hours

6.3% 25°C

Long term stability of the analyte stock solution 15 days 8.6% 4°C


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CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 Long term stability of stock internal standard solution 15 days

9.7% 4°C

Long term stability of working internal standard solution 15 days 7.4% 4°C

Short-term stability in plasma at room temperature (QC) 4 hours % -1.6 to

4.9

Short-term stability in plasma at room temperature (I.S.) 4 hours % -3.9 to

0.5

Post-preparative stability (dry extract stability) N/A

Long term stability in plasma 288 days

-6.1 to 11.0 -25°C

Autosampler storage stability 24 hours -7.8 to -4.0

Freeze and thaw stability (-25 °C) 3 cycles -5.9 to

8.8

Dilution integrity Concentration diluted 2-fold, Accuracy 0.9 % Precision 8.6 % Concentration diluted 3-fold, Accuracy -0.6 % Precision 9.4 %

DG3173 Analytical Validation Report CEPHA archive This analytical method was used in the following studies:

CPA 430-13

Short description of the method LC-MS/MS Biological matrix

K3EDTA human plasma

Analyte DG 3173 Internal standard (I.S.) Cisapride monohydrate Calibration range (ng/mL) 0.12 - 474.09 Linearity (Correlation Coefficient)

0.997136

Lower limit of quantification (LLOQ) - Accuracy (%)

0.0

Lower limit of quantification (LLOQ) - Precision (%)

5.3


20


Standard curve concentrations (ng/mL) 0.12; 0.72; 2.51; 8.78; 26.34; 79.02; 237.05; 474.09

QC concentrations (ng/mL) 0.33; 239.33; 382.92

Between-run accuracy QC LLOQ % 1.7 Between-run accuracy QC low, mid, high % -7.3 to 3.6

Between-run precision QC LLOQ % 12.2 Between-run precision QC low, mid, high % 6.1

Within-run accuracy QC LLOQ % 6.9 Within-run accuracy QC low, mid, high % 0.4 to 5.1

Within-run precision QC LLOQ % 5.9 Within-run precision QC low, mid, high % 8.4

Matrix Factor % (Analyte low conc.) 91.8

Matrix Factor % (Analyte high conc.) 96.5 Matrix Factor % (I.S.) 96.4 CV% of IS-normalised matrix factor at low conc. 3.7 CV% of IS-normalised matrix factor at high conc. 3.9

Short term stability of working internal standard solution

6 hours 6.3% 25°C

Long term stability of the analyte stock solution

15 days 14.7% 4°C

Long term stability of stock internal standard solution

15 days 7.4% 4°C

Long term stability of working internal standard solution

15 days 7.4% 4°C

Short-term stability in plasma at room temperature (QC)%

4 hours -3.0 to -1.2

Short-term stability in plasma at room temperature (I.S.)%

4 hours 2.0 to 7.7

Post-preparative stability (dry extract stability) N/A

Long term stability in plasma

288 days -13.2 to 2.0 % -25°C

Autosampler storage stability 24 hours 1.2 to 6.1

Freeze and thaw stability (-25 °C) 3 cycles 3.3 to 9.1

Dilution integrity

Concentration diluted 2-fold, Accuracy 2.1 % Precision 8.2 % Concentration diluted 3-fold, Accuracy 1.4 % Precision 8.8 %


21

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 See Appendix IV of the Guideline: Table 4.2 Storage period of study samples

Study ID and analyte

Longest storage period CPA 430-13, DG3173, OCT

106 days at temperature -25°C

See Appendix IV of the Guideline: Table 4.3 Sample analysis of CPA 430-13 Study ID and analyte CPA 430-13

Octreotide and DG3173 Total numbers of collected samples 84

Total number of samples with valid results 84

Total number of reassayed samples1,2 0

Total number of analytical runs1 1

Total number of valid analytical runs1 1

Incurred sample reanalysis Number of samples N/A

Percentage of samples where the difference between the two values was less than 20% of the mean N/A 1 Without incurred samples 2 Due to other reasons than not valid run


22

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 13 In-Study Validation In-Study validation cannot be evaluated for one analytical run, which was assayed in study CPA 430-13. The results obtained follow: 13.1 Back Calculated Lower Limit of Quantification (LLOQ) 13.1A Back Calculated Lower Limit of Quantification (LLOQ) of Octreotide

% Relative Error within ±20% and CV % ≤20% of the nominal value of LLOQ were observed. It was concluded that LLOQ used within overall plasma samples bioassay was acceptable as for accuracy and precision. Details see Table 3A: Summary of Back-calculated Calibration Standards of Octreotide. 13.1B Back Calculated Lower Limit of Quantification (LLOQ) of DG3173

% Relative Error within ±20% and CV % ≤20% of the nominal value of LLOQ were observed. It was concluded that LLOQ used within overall plasma samples bioassay was acceptable as for accuracy and precision. Details see Table 3B: Summary of Back-calculated Calibration Standards of DG3173. 13.2 Precision and Accuracy 13.2.1 Overall Between-run Precision (CV) 13.2.1A Overall Between-run Precision (CV) of Octreotide

Overall CV % ≤15% of the nominal values of all QC standards was observed. It was concluded that precision (CV) found within plasma samples bioassay was acceptable. Details see Table 4A: Summary of Back-calculated QC Standards of Octreotide.

LLOQ nominal value LLOQ value Rel. Error of LLOQ CV of LLOQ

[ng/mL] [ng/mL] [%] [%]

Octreotide LLOQ 0.13 N/A N/A N/A

LLOQ nominal value LLOQ value Rel. Error of LLOQ CV of LLOQ

[ng/mL] [ng/mL] [%] [%]

DG3173 LLOQ 0.12 0.12 N/A N/A

CV Average CV[%] [%]

Octreotide QC Standards N/A N/A


23

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 13.2.1B Overall Between-run Precision (CV) of DG3173

Overall CV % ≤15% of the nominal values of all QC standards was observed. It was concluded that precision (CV) found within plasma samples bioassay was acceptable. Details see Table 4B: Summary of Back-calculated QC Standards of DG3173. 13.2.2 Overall Between-run Accuracy (Rel. Error) 13.2.2A Overall Between-run Accuracy (Rel. Error) of Octreotide

Overall %Rel. Error ±15% of the nominal values of all QC standards was observed. It was concluded that accuracy (Rel. Error) found within plasma samples bioassay was acceptable. Details see Table 4A: Summary of Back-calculated QC Standards of Octreotide.

13.2.2B Overall Between-run Accuracy (Rel. Error) of DG3173

Overall %Rel. Error ±15% of the nominal values of all QC standards was observed. It was concluded that accuracy (Rel. Error) found within plasma samples bioassay was acceptable. Details see Table 4B: Summary of Back-calculated QC Standards of DG3173.

13.3 Calibration Curves Correlation Coefficient 13.3A Calibration Curves Correlation Coefficient of Octreotide

Correlation coefficient ≥0.990 of all calibration curves in study CPA 430-13 was observed. It was concluded that correlation coefficient found within overall plasma samples bioassay was acceptable. Details see Table 2A: Calibration Curves Summary of Octreotide.

CV Average CV[%] [%]

DG3173 QC Standards N/A N/A

Rel. Error Average Rel. Error[%] [%]

Octreotide QC Standards N/A N/A

Rel. Error Average Rel. Error[%] [%]

DG3173 QC Standards N/A N/A

Corelation Coefficient

(average)Octreotide Calibration Curve 0.998308


24

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 13.3B Calibration Curves Correlation Coefficient of DG3173

Correlation coefficient ≥0.990 of all calibration curves in study CPA 430-13 was observed. It was concluded that correlation coefficient found within overall plasma samples bioassay was acceptable. Details see Table 2B: Calibration Curves Summary of DG3173. 13.4 Long-term Stability The first blood sample was collected on June 10, 2013. The last sample was assayed on September 24, 2013, see Table 1. Time between those dates represented 106 days. Long-term stability of Octreotide and DG3173 in plasma samples tested in pre-study validation was 288 days at temperature -25°C (range -20°C to -35°C). Therefore, long-term stability time period validated within pre-study validation covered whole time, when the study plasma samples were stored and analyzed. Taking into consideration all results mentioned above, it can be concluded, that the validated bioanalytical method SOP CPA MET 125-02 was reliable for determination of Octreotide and DG3173 in plasma samples obtained in Phase I study. 14 In-Study Descriptive Statistics 14.1 In-Study Back Calculated Calibration Standards Summary 14.1A In-Study Back Calculated Calibration Standards Summary of Octreotide

There was % Dev. ≤20% of the nominal value of LLOQ (S8), % Dev. ≤10% of the nominal value of ULOQ (S1) and % Dev. ≤15% of the nominal values of mid calibration standards (S7 – S2) observed. It was concluded that deviations of calibration standards found within plasma samples bioassay were acceptable.

Corelation Coefficient

(average)DG3173 Calibration Curve 0.996947

Octreotide Calibration StandardsS8 S7 S6 S5 S4 S3 S2 S1

Amount Added [ng/mL]0.13 0.75 2.64 9.24 27.72 83.16 249.49 498.97

n 1 0 1 1 1 1 1 1

Amount found ng/mL 0.13 EC 2.76 9.75 25.28 88.12 235.15 506.17% Deviation -0.3 EC 4.4 5.6 -8.8 6.0 -5.7 1.4


25

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 14.1B In-Study Back Calculated Calibration Standards Summary of DG3173

There was % Dev. ≤20% of the nominal value of LLOQ (S8), % Dev. ≤10% of the nominal value of ULOQ (S1) and % Dev. ≤15% of the nominal values of mid calibration standards (S7 – S2) observed. It was concluded that deviations of calibration standards found within plasma samples bioassay were acceptable. 14.2 In-Study Back Calculated QC Standards Summary 14.2A In-Study Back Calculated QC Standards Summary of Octreotide

There was % Dev. ≤15% of the nominal value of all QC standards observed. It was concluded that deviation of QC standards found within plasma samples bioassay were acceptable. 14.2B In-Study Back Calculated QC Standards Summary of DG3173

There was % Dev. ≤15% of the nominal value of all QC standards observed. It was concluded that deviation of QC standards found within plasma samples bioassay were acceptable.

DG3173 Calibration StandardsS8 S7 S6 S5 S4 S3 S2 S1

Amount Added [ng/mL]0.12 0.72 2.51 8.78 26.34 79.02 237.05 474.09

n 1 1 0 1 1 1 1 1

Amount found ng/mL 0.12 0.77 EC 8.48 23.66 77.30 258.19 461.91% Deviation -1.1 6.9 EC -3.5 -10.2 -2.2 8.9 -2.6

QC 3 0.34 QC 2 245.03 QC 1 392.05n 2 2 2Amount found [ng/mL] 0.33 257.50 394.30% Dev. -3.0 5.1 0.6Amount found [ng/mL] 0.36 224.26 430.40% Dev. 7.2 -8.5 9.8

Octreotide Amount Added [ng/mL]

QC 3 0.33 QC 2 239.33 QC 1 382.92n 2 2 2Amount found [ng/mL] 0.34 258.39 379.62% Dev. 4.3 8.0 -0.9Amount found [ng/mL] 0.31 253.51 387.26% Dev. -5.2 5.9 1.1

DG3173 Amount Added [ng/mL]


26

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 The detailed information on in-study validation result, in-study descriptive statistic is given in following tables: Table 1: Analytical Runs Schedule of Octreotide and DG3173 Table 2A: Calibration Curves Summary of Octreotide Table 2B: Calibration Curves Summary of DG3173 Table 3A: Summary of Back-calculated Calibration Standards of Octreotide Table 3B: Summary of Back-calculated Calibration Standards of DG3173 Table 4A: Summary of Back-calculated QC Standards of Octreotide Table 4B: Summary of Back-calculated QC Standards of DG3173 Table 5A: Summary of Calibration Standards Accuracy of Octreotide Table 5B: Summary of Calibration Standards Accuracy of DG3173


27

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 15 Document Archiving All raw and calculated data related to the bioassay of Octreotide and DG3173 are stored in electronic form as a hard copy and a back-up copy in two separate archive places. Chromatograms and Validation Report related to the bioassay of Octreotide and DG3173 are stored in printed form in the CEPHA archives. CEPHA s.r.o. will retain complete study documentation for at least 15 years after the completion of the study. Then the Sponsor will be asked to determine in writing whether the documentation is to be discarded or shipped to the Sponsor. During the storage period, the documentation will be available for inspection if requested by Sponsor or a properly authorized employee of the domestic or foreign regulatory authorities in accordance with the Czech law. 16 References Bioanalytical Study Plan 430-13, Final Version / September 3, 2013. SOP CPA MET 125-02: LC-MS/MS determination of Octreotide and DG3173 in human plasma Bioassay Method Validation Report, Version 03, 11.01.2013, CPA MET 125-02, Octreotide (0.13 – 498.97 ng/mL) and DG3173 (0.12 – 474.09 ng/mL). FDA Guidance for Industry. Bioanalytical Method Validation. May 2001. CHMP Guideline on bioanalytical method validation, EMEA/CHMP/EWP/192217/2009, London, 21 July 2011. Appendix IV of the Guideline CHMP Guideline on the Investigation of Bioequivalence, CPMP/EWP/QWP/1401/98 Rev. 1, Presentation of Biopharmaceutical and Bioanalytical Data in Module 2.7.1, June 2012.


28


TABLES


29


Table 1. Study 430-13: Analytical Runs Schedule of Octreotide and DG3173

Run Date Result(dd/mm/yy)

RUN 01 24/09/13 accepted

Table 2A. Study 430-13: Calibration Curves Summary of Octreotide

Coeff.Run Equation of Correlation

Y = B2*X2 + B1*X + B0 Determin. Coefficient (r2) (r)

RUN 01 Y = 5.09227E-06 * X2 + 0.00130063 * X + 0.000546983 0.996618 0.998308

Table 2B. Study 430-13: Calibration Curves Summary of DG3173

Coeff.Run Equation of Correlation

Y = B2*X2 + B1*X + B0 Determin. Coefficient (r2) (r)

RUN 01 Y = 1.74794E-06 * X2 + 0.000544294 * X + 0.000655891 0.993903 0.996947


30


Table 3A. Study 430-13: Summary of Back-calculated Calibration Standards

of Octreotide

Calibration Standards

S8 S7 S6 S5 S4 S3 S2 S1

Amount Added [ng/mL]

0.13 0.75 2.64 9.24 27.72 83.16 249.49 498.97

n 1 0 1 1 1 1 1 1

Amount found ng/mL 0.13 EC 2.76 9.75 25.28 88.12 235.15 506.17

Mean N/A N/A N/A N/A N/A N/A N/A N/A

Std. Dev. N/A N/A N/A N/A N/A N/A N/A N/A

% CV N/A N/A N/A N/A N/A N/A N/A N/A

% Rel. Error N/A N/A N/A N/A N/A N/A N/A N/A

min N/A N/A N/A N/A N/A N/A N/A N/Amax N/A N/A N/A N/A N/A N/A N/A N/A

Table 3B. Study 430-13: Summary of Back-calculated Calibration Standards

of DG3173


S8 S7 S6 S5 S4 S3 S2 S1


0.12 0.72 2.51 8.78 26.34 79.02 237.05 474.09

n 1 1 0 1 1 1 1 1

Amount found ng/mL 0.12 0.77 EC 8.48 23.66 77.30 258.19 461.91

Mean N/A N/A N/A N/A N/A N/A N/A N/A

Std. Dev. N/A N/A N/A N/A N/A N/A N/A N/A

% CV N/A N/A N/A N/A N/A N/A N/A N/A

% Rel. Error N/A N/A N/A N/A N/A N/A N/A N/A

min N/A N/A N/A N/A N/A N/A N/A N/Amax N/A N/A N/A N/A N/A N/A N/A N/A


31


Table 4A. Study 430-13: Summary of Back-calculated QC Standards of Octreotide


Run QC 3 0.34 QC 2 245.03 QC 1 392.05

( Allowance ) ( Allowance ) ( Allowance )0.29 0.39 208.28 281.78 333.24 450.86

RUN 01 0.33 257.50 394.30 0.36 224.26 430.40

n 2 2 2Mean N/A N/A N/AStd. Dev. N/A N/A N/A% CV N/A N/A N/A% Rel. Error N/A N/A N/A

Table 4B. Study 430-13: Summary of Back-calculated QC Standards of DG3173


Run QC 3 0.33 QC 2 239.33 QC 1 382.92

( Allowance ) ( Allowance ) ( Allowance )0.28 0.38 203.43 275.23 325.48 440.36

RUN 01 0.34 258.39 379.62 0.31 253.51 387.26

n 2 2 2Mean N/A N/A N/AStd. Dev. N/A N/A N/A% CV N/A N/A N/A% Rel. Error N/A N/A N/A


32


Table 5A. Study 430-13: Summary of Calibration Standards Accuracy of Octreotide

Percent of Relative Error of Calibration Standards


S8 S7 S6 S5 S4 S3 S2 S1

RUN 01 -0.3 EC 4.4 5.6 -8.8 6.0 -5.7 1.4

* Rel. Error is calculated automaticaly by TargetLynx using more decimal places of concentration

values than presented.

Run

Table 5B. Study 430-13: Summary of Calibration Standards Accuracy of DG3173

Percent of Relative Error of Calibration Standards


S8 S7 S6 S5 S4 S3 S2 S1

RUN 01 -1.1 6.9 EC -3.5 -10.2 -2.2 8.9 -2.6

* Rel. Error is calculated automaticaly by TargetLynx using more decimal places of concentration

values than presented.

Run


33

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 Table 6. Evaluated Subject Concentration Data of Octreotide and DG3173

subject sample studyday sampling OCT conc. DG conc.no. no. time point ng/mL ng/mL

1.01 101 1 predose1.01 102 1 60' 47.971.01 201 5 predose1.01 202 5 60' 14.031.01 301 10 predose1.01 302 10 60' 28.441.01 401 14 predose1.01 402 14 60'1.01 501 18 predose1.01 502 18 60' 143.161.02 101 1 predose1.02 102 1 60' 31.421.02 201 5 predose1.02 202 5 60'1.02 301 10 predose1.02 302 10 60' 158.111.02 401 14 predose1.02 402 14 60' 11.791.02 501 18 predose1.02 502 18 60' 56.231.03 101 1 predose1.03 102 1 60'1.03 201 5 predose1.03 202 5 60' 95.111.03 301 10 predose1.03 302 10 60' 60.721.03 401 14 predose1.03 402 14 60' 14.711.03 501 18 predose1.03 502 18 60' 19.691.04 101 1 predose1.04 102 1 60' 107.101.04 201 5 predose1.04 202 5 60' 19.471.04 301 10 predose1.04 302 10 60' 73.221.04 401 14 predose1.04 402 14 60'1.04 501 18 predose1.04 502 18 60' 27.48

STUDY CPA 430-13 (DG3173-I-003 )page 1


34

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 Table 6. Evaluated Subject Concentration Data of Octreotide and DG3173 Continued


1.05 101 1 predose1.05 102 1 60' 88.221.05 101 1 REPE predose1.05 102 1 REPE 60' 81.011.05 201 5 predose1.05 202 5 60'1.05 301 10 predose1.05 302 10 60' 130.551.05 401 14 predose1.05 402 14 60' 17.821.05 501 18 predose1.05 502 18 60' 55.291.06 101 1 predose1.06 102 1 60' 18.651.06 201 5 predose1.06 202 5 60' 39.721.06 301 10 predose1.06 302 10 60' 68.981.06 401 14 predose1.06 402 14 60'1.06 501 18 predose1.06 502 18 60' 128.231.07 101 1 predose1.07 102 1 60' 73.151.07 101 1 REPE predose1.07 102 1 REPE 60' 154.451.07 201 5 predose1.07 202 5 60'1.07 301 10 predose1.07 302 10 60' 34.391.07 401 14 predose1.07 402 14 60' 13.801.07 501 18 predose1.07 502 18 60' 68.07



35

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 Table 6. Evaluated Subject Concentration Data of Octreotide and DG3173 Continued


1.08 101 1 predose1.08 102 1 60' 32.821.08 201 5 predose1.08 202 5 60' 23.341.08 301 10 predose1.08 302 10 60' 79.051.08 401 14 predose1.08 402 14 60'1.08 501 18 predose1.08 502 18 60' 187.12



36

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 Table 7. Bioassay Data


37

Quantify Compound Summary Report Masslynx 4.1 SCN 843 Page 1 of 9 CPA_430_13

Dataset: C:\Masslynx\CPA 430-13.PRO\RUN 01.qld

Last Altered: Tuesday, October 15, 2013 09: 11: 13 Central Europa Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Central Europa Daylight Time

By CEPHA\dohalsky (Vaclav Dohalsky)

Method: C:\Masslynx\CPA 430-13.PRO\MethDB\RUN 01.mdb 15 Oct 2013 08:41 :32 Calibration: C:\Masslynx\CPA 430-13.PRO\CurveDB\RUN 01.cdb 15 Oct 2013 09: 11 :13

Compound name: OCT Coefficient of Determination: Rl\2 = 0.996618 Calibration curve: 5.09227e-006 * xA2 + 0.00130063 * x + 0.000546983 Response type: Interna! Std ( Ref 3 ), Area * ( IS Conc. / IS Area ) Curve type: 2nd Order, Origin: Exclude, Weighting: 1/xl\2, Axis trans: None

1 1: 1 RUN 01_Blank Blank O.O

2 1:2 RUN 01_SO Analyte 1527274 O.O

3 1:3 RUN 01_S8 Standard 0.13 2.24 1444 2017119 0.00072 0.13 -0.3 1.0 bb YES

4 1:4 RUN 01_S7 Standard 0.75 2.23 3301 1697087 0.00194 1.07 42.7 1.0 bbX YESb C,., ''(J/1J

5 1:5 RUN 01_S6 Standard 2.64 2.26 8766 2102593 0.00417 2.76 4.4 1.0 bb YES






11 1:11 RUN 01_QC3a QC 0.34 2.28 2379 2436259 0.00098 0.33 -3.0 O.O bb YES

12 1:12 RUN 01_101101 Analyte 2012917 O.O

13 1:13 RUN 01_101102 Analyte 2498241 o.o 141:14 RUN01_101201 Analyte 2114569 O.O

15 1:15 RUN 01_101202 Analyte 2.26 40394 2040328 0.01980 14.03 O.O bb YES

16 1:16 RUN 01_101301 Analyte 1828955 O.O

17 1:17 RUN 01_101302 Analyte 2070224 O.O

18 1:18 RUN 01_101401 Analyte 1834925 o.o 19 1:19 RUN 01_101402 Analyte 1974365 o.o 20 1 :20 RUN 01_ 101501 Analyte 1916816 O.O

21 1:21 RUN 01_101502 Analyte 2018840 o.o 22 1:22 RUN 01_102101 Analyte 1441222 o.o 23 1:23 RUN 01_102102 Analyte 2167450 o.o 24 1 :24 RUN 01_ 102201 Analyte 1276899 o.o 25 1:25 RUN 01_102202 Analyte 3209654 ~Le=- 0J)l6Jfvj >;: 26 1:26 RUN 01_102301 Analyte 2160598 O.O

27 1:27 RUN 01_102302 Analyte 1862099 O.O

28 1 :28 RUN 01_ 102401 Analyte 1524693 o.o 29 1 :29 RUN 01_QC2b QC 245.03 2.28 1279976 1901631 0.67309 257.50 5.1 O.O bb YES


31 1:31 RUN 01_102501 Analyte 2766886 o.o 32 1:32 RUN 01_102502 Analyte 2561494 O.O

33 1:33 RUN 01_103101 Analyte 1912880 O.O

34 1:34 RUN 01_103102 Analyte 1555503 O.O

35 1 :35 RUN 01_ 103201 Analyte 2098456 O.O

361:36 RUN01_103202 Analyte 2452424 O.O

371:37 RUN01_103301 Analyte 1344907 o.o 38 1:38 RUN 01_103302 Analyte 2576214 o.o 391:39 RUN01_103401 Analyte 2170882 O.O

401:40 RUN01_103402 Analyte 2.32 44781 2154267 0.02079 14.71 O.O bb YES

Vř

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CPA_430_13


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Compoundname:OCT

41 1:41 RUN 01_103501 Analyte 1912483 O.O

42 1:42 RUN 01_103502 Analyte 2722625 O.O

43 1:43 RUN 01_104101 Analyte 1797718 O.O

441:44 RUN01_104102 Analyte 2090878 O.O

45 1 :45 RUN 01_ 104201 Analyte 1569367 O.O


47 1:47 RUN 01_QC1c QC 392.05 2.32 2369406 1815498 1.30510 394.30 0.6 o.o bb YES

481:48 RUN01_104301 Analyte 2392957 o.o 49 2:1 RUN 01_ 104302 Analyte 1575062 O.O

50 2:2 RUN 01_ 104401 Analyte 1838068 O.O

51 2:3 RUN 01_104402 Analyte 1690903 O.O

52 2:4 RUN 01_104501 Analyte 1918707 o.o 53 2:5 RUN 01_ 104502 Analyte 1872050 O.O

54 2:6 RUN 01_ 105101 Analyte 1529741 o.o 55 2:7 RUN 01_ 105102 Analyte 1066569 o.o 56 2:8 RUN 01_ 105101 REPE Analyte 1434944 O.O

57 2:9 RUN 01_ 105102REPE Analyte 1534558 O.O


60 2:12 RUN 01_105301 Analyte 1709661 O.O

61 2:13 RUN 01_105302 Analyte 1518660 O.O

62 2:14 RUN 01_105401 Analyte 1764999 O.O


64 2:16 RUN01_105501 Analyte 1200370 O.O

65 2:17 RUN 01_QC3d QC 0.34 2.36 2456 2403881 0.00102 0.36 7.2 o.o bb YES



69 2:21 RUN 01_ 106201 Analyte 1512339 O.O

70 2:22 RUN 01_106202 Analyte 1690855 O.O

71 2:23 RUN 01_ 106301 Analyte 1597068 O.O

72 2:24 RUN 01_106302 Analyte 1650710 o.o 73 2:25 RUN 01_ 106401 Analyte 2246457 o.o 74 2:26 RUN 01_ 106402 Analyte 1831558 O.O

75 2:27 RUN 01_ 106501 Analyte 1805932 o.o 76 2:28 RUN 01_ 106502 Analyte 1839884 O.O

77 2:29 RUN 01_ 107101 Analyte 1643989 o.o 78 2:30 RUN 01_ 107102 Analyte 1078417 O.O

79 2:31 RUN 01_ 107101 REPE Analyte 1795434 O.O

80 2:32 RUN 01_ 107102REPE Analyte 2001187 o.o 81 2:33 RUN 01_ 107201 Analyte 1256443 O.O

82 2:34 RUN 01_ 107202 Analyte 1569969 o.o 83 2:35 RUN 01_QC2e QC 245.03 2.27 1008891 1839908 0.54834 224.26 -8.5 O.O bb YES

84 2:36 RUN 01_107301 Analyte 1132307 O.O

85 2:37 RUN 01_107302 Analyte 1469643 O.O

86 2:38 RUN 01_ 107401 Analyte 1381822 O.O

87 2:39 RUN 01_ 107402 Analyte 2.28 31067 1595754 0.01947 13.80 o.o bb YES

«

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Compound name: OCT

88 2:40 RUN 01_107501 Analyte 1252991 O.O 89 2:41 RUN 01_ 107502 Analyte 1225056 O.O 90 2:42 RUN 01_ 108101 Analyte 1465096 o.o 91 2:43 RUN 01_ 108102 Analyte 1697370 o.o 92 2:44 RUN 01_ 108201 Analyte 1759233 O.O

93 2:45 RUN 01_ 108202 Analyte 2.33 54067 1605532 0.03368 23.34 O.O bb VES

94 1:12 RUN 01_108301 Analyte 1133264 O.O

95 1:13 RUN 01_108302 Analyte 1269405 O.O

96 1:14 RUN 01_ 108401 Analyte 1142853 O.O

97 1:15 RUN 01_108402 Analyte 1357313 O.O

98 1:16 RUN 01_108501 Analyte 1977808 o.o 99 1:17 RUN 01_108502 Analyte 1918168 o.o

100 1:18 RUN 01_QC1f QC 392.05 2.35 3157089 2099649 1.50363 430.40 9.8 O.O bb VES

r

40

Quantify Compound Summary Report Masslynx 4.1 SCN 843 CPA_430_13


Last Altered: Tuesday, October 15, 2013 09: 11: 13 Centra I Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Central Europe Daylight Time


Compound name: DG Coefficient of Determination: RA2 = 0.993903 Calibration curve: 1.74794e-006 * xA2 + 0.000544294 * x + 0.000655891 Response type: Interna! Std ( Ref 3 ), Area * ( IS Conc. / IS Area ) Curve type: 2nd Order, Origin: Exclude, Weighting: 1/xA2, Axis trans: None

1 1:1 RUN 01_Blank

2 1:2 RUN 01_SO

3 1:3 RUN 01_S8

4 1:4 RUN 01_S7

5 1:5 RUN 01_S6

6 1:6 RUN 01_S5

7 1:7 RUN 01_S4

8 1 :8 RUN 01_S3

9 1 :9 RUN 01_S2

101:10 RUN01_S1

11 1:11 RUN 01_QC3a

12 1:12 RUN 01_101101

13 1:13 RUN 01_101102

14 1:14 RUN 01_101201

15 1:15 RUN 01_101202

16 1:16 RUN 01_101301

17 1:17 RUN 01_101302

18 1:18 RUN 01_101401

19 1:19 RUN 01_101402

20 1:20 RUN 01_101501

21 1:21 RUN 01_101502

22 1:22 RUN 01_102101

23 1:23 RUN 01_102102

24 1:24 RUN 01_102201

251:25 RUN01_102202

261:26 RUN01_102301

271:27 RUN01_102302

281:28 RUN01_102401

29 1:29 RUN 01_QC2b

301:30 RUN01_102402

31 1:31 RUN 01_ 102501

321:32 RUN01_102502

331:33 RUN01_103101

341:34 RUN01_103102

351:35 RUN01_103201

361:36 RUN01_103202

37 1 :37 RUN 01_ 103301

38 1:38 RUN 01_103302

39 1 :39 RUN 01_ 103401

40 1:40 RUN 01_103402

41 1:41 RUN 01_103501

42 1:42 RUN 01_103502

43 1:43 RUN 01_104101

44 1:44 RUN 01_104102

Blank

Analyte

Standard

Standard

Standard

Standard

Standard

Standard

Standard

Standard

QC

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

QC

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

0.12 2.41

0.72 2.42

2.51 2.42

8.78 2.43

26.34 2.42

79.02 2.43

237.05 2.43

474.09 2.44

0.33 2.42

2.44

2.46

2.46

2.46

2.49

239.33 2.46

2.52

2.52

2.54

2.53

2.54

1453

1826

3674

8544

41092

95171

1527274

2017119

1697087

2102593

1583843

2830985

1789784

0.00072

0.00108

0.00175

0.00539

0.01452

0.05317

407290 1580409 0.25771

1161611 1858567 0.62500

2055 2436259 0.00084

2012917

76922 2498241 0.03079

2114569

2040328

1828955

36337 2070224 0.01755

1834925

1974365

1916816

230950 2018840 0.11440

1441222

42232 2167450 0.01948

1276899

3209654

2160598

242840 1862099 0.13041

1524693

490611 1901631 0.25799

2215767

2766886

94227 2561494 0.03679

1912880

1555503

2098456

167338 2452424 0.06823

1344907

103439 2576214 0.04015

2170882

2154267

1912483

32808 2722625 0.01205

1797718

165170 2090878 0.07900

0.12 -1.1

0.77 6.9

1.99 -20.6

8.48 -3.5

23.66 -10.2

77.30 -2.2

258.19 8.9

461.91 -2.6

0.34 4.3

47.97

28.44

143.16

31.42

158.11

258.39 8.0

56.23

95.11

60.72

19.69

107.10

O.O

O.O

1.0 bd

1.0 bd

1.0 bdX

1.0 bd

1.0 bb

1.0 bb

1.0 bb

1.0 bb

o.o bd

O.O

O.O bb

o.o O.O

O.O

O.O bb

o.o O.O

o.o O.O bb

O.O

O.O bb

o.o

Page 4 of 9

YES

YES

YESb

YES

YES

YES

YES

YES

YES

YES

YES

YES

YES

~LE o. o -!Jjli IJ i) O.O "'G> O.O bb YES

O.O

O.O bb YES

O.O

o.o O.O bb

o.o O.O

o.o O.O bb

o.o O.O bb

O.O

O.O

O.O

o.o bb

O.O

o.o bb

YES

YES

YES

YES

YES

41

Quantify Compound Summary Report MassLynx 4.1 SCN 843 CPA_430_13




Compound name: DG

45 1:45 RUN 01_104201

461:46 RUN01_104202

47 1:47 RUN 01_QC1c

481:48 RUN01_104301

49 2:1 RUN 01_104302

50 2:2 RUN 01_ 104401

51 2:3 RUN 01_ 104402

52 2:4 RUN 01_ 104501

53 2:5 RUN 01_ 104502

54 2:6 RUN 01_105101

55 2:7 RUN 01_ 105102

56 2:8 RUN 01_105101REPE

57 2:9 RUN 01_ 105102REPE

58 2:10 RUN 01_ 105201

59 2:11 RUN 01_105202

60 2:12 RUN 01_105301

61 2:13 RUN01_105302

62 2:14 RUN 01_105401

63 2:15 RUN 01_105402

64 2:16 RUN 01_ 105501

65 2:17 RUN 01_QC3d

66 2:18 RUN 01_105502

67 2:19 RUN 01_106101

68 2:20 RUN 01_ 106102

69 2:21 RUN 01_ 106201

70 2:22 RUN 01_106202

71 2:23 RUN 01_ 106301

72 2:24 RUN 01_ 106302

73 2:25 RUN 01_ 106401

74 2:26 RUN 01_ 106402

75 2:27 RUN 01_ 106501

76 2:28 RUN 01_106502

77 2:29 RUN 01_107101

78 2:30 RUN 01_ 107102

79 2:31 RUN 01_ 107101 REPE

80 2:32 RUN 01_ 107102REPE

81 2:33 RUN 01_ 107201

82 2:34 RUN 01_ 107202

83 2:35 RUN 01_QC2e

84 2:36 RUN 01_ 107301

85 2:37 RUN 01_107302

86 2:38 RUN 01_ 107401

87 2:39 RUN 01_ 107402

88 2:40 RUN 01_ 107501

89 2:41 RUN 01_ 107502

90 2:42 RUN 01_ 108101

91 2:43 RUN 01_ 108102

Analyte

Analyte

QC

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

QC

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

QC

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

Analyte

382.92 2.56

2.53

2.53

2.53

2.53

2.54

0.33 2.50

2.53

2.48

2.54

2.50

2.53

2.52

239.33 2.45

2.46

2.54

2.53

1569367

2289054

833645 1815498 0.45918

2392957

78560 1575062 0.04988

1838068

1690903

1918707

31697 1872050 0.01693

1529741

66422 1066569 0.06228

1434944

86276 1534558 0.05622

1539134

1167856

1709661

154152 1518660 0.10151

1764999

1685858

1200370

1986 2403881 0.00083

41132 1139684 0.03609

1738780

1756369

1512339

42327 1690855 0.02503

1597068

76786 1650710 0.04652

2246457

1831558

1805932

182493 1839884 0.09919

1643989

53735 1078417 0.04983

1795434

252995 2001187 0.12642

1256443

1569969

461765 1839908 0.25097

1132307

31509 1469643 0.02144

1381822

1595754

1252991

56112 1225056 0.04580

1465096

34630 1697370 0.02040

379.62 -0.9

73.22

27.48

88.22

81.01

130.55

0.31 -5.2

55.29

39.72

68.98

128.23

73.15

154.45

253.51 5.9

34.39

68.07

32.82

O.O

O.O

O.O bb

O.O

o.o bb

O.O

O.O

O.O

o.o bb

O.O

o.o bb

O.O

O.O bb

O.O

o.o O.O

O.O db

O.O

o.o O.O

O.O bb

O.O db

O.O

O.O

O.O

o.o db

O.O

o.o db

O.O

O.O

O.O

o.o bb

O.O

O.O bd

o.o o.o bb

o.o o.o O.O bb

O.O

O.O bb

O.O

o.o O.O

o.o bb

O.O

o.o bb

Page 5 of 9

YES

YES

YES

YES

YES

YES

YES

YES

YES

YES

YES

YES

YES

YES

YES

YES

YES

42

Quantify Compound Summary Report MassLynx 4.1 SCN 843 Page 6 of 9 CPA_ 430_13




Compound name: DG

..• )•S/tU,OQ 92 2:44 RUN 01_108201 Analyte 1759233 O.O

93 2:45 RUN 01_ 108202 Analyte 1605532 o.o 941:12 RUN01_108301 Analyte 1133264 o.o 95 1:13 RUN 01_108302 Analyte 2.53 69320 1269405 0.05461 79.05 o.o bd YES 961:14 RUN01_108401 Analyte 1142853 O.O


99 1:17 RUN 01_108502 Analyte 2.57 314018 1918168 0.16371 187.12 O.O bb YES 100 1:18 RUN 01_QC1f QC 382.92 2.69 994333 2099649 0.47357 387.26 1.1 O.O bb YES

~

43

CEPHA s.r.o. Study Code: CPA 430-13 Page Sponsor’s Study Code: DG3173-I-003 Appendix 1 The copies of chromatograms of complete run RUN 01 are enclosed.


44

Quantify Calibration Report Masslynx 4.1 SCN 843 CPA_430_13


Last Altered: Tuesday, October 15, 2013 09:11 :13 Centra! Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Centra! Europe Daylight Time


Method: C:\Masslynx\CPA 430-13.PRO\MethDB\RUN 01.mdb 15 Oct 2013 08:41 :32 Calibration: C:\Masslynx\CPA 430-13.PRO\CurveDB\RUN 01.cdb 15 Oct 2013 09:11:13

Compound name: OCT Coefficient of Determination: R"2 = 0.996618 Calibration curve: 5.09227e-006 * x"2 + 0.00130063 * x + 0.000546983 Response type: Interna! Std ( Ret 3 ), Area * ( IS Conc. / IS Area ) Curve type: 2nd Order, Origin: Exclude, Weighting: 1/x"2, Axis trans: None

Page 1of3

X

20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460 480 ~ly

45

Quantify Calibration Report Masslynx 4.1 SCN 843 CPA_430_13




Compound name: DG Coefficient of Determination: R"2 = 0.993903 Calibration curve: 1.74794e-006 * x"2 + 0.000544294 * x + 0.000655891 Response type: Interna! Std ( Ret 3 ), Area * ( IS Conc. / IS Area ) Curve type: 2nd Order, Origin: Exclude, Weighting: 1/x"2, Axis trans: None

X

Page 2 of 3

~

X

ng/ml 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460 r

46

Quantify Sample Report CPA_430_13

Masslynx 4.1 SCN 843


Last Altered: Tuesday, October 15, 2013 09:11 :13 Centra! Europe DaylightTime Printed: At Tuesday, October 15, 2013 09: 12:04 Centra! Europe Daylight Time


Method: C:\Masslynx\CPA 430-13.PRO\MethDB\RUN 01.mdb 15 Oct 2013 08:41:32 Calibration: C:\Masslynx\CPA 430-13.PRO\CurveDB\RUN 01.cdb 15 Oct 2013 09:11:13

Name: RUN 01_Blank, Date: 24-Sep-2013, Time: 15:43:11, Vial: 1:1

OCT RUN 01_Blank

1.81

90

%

3.43

2.33

~o m~ 2.00 2.25 2.50 2.75 3.00 3.25

DG RUN 01_Blank

1.81

90

%

2.30

2.74 2.93 3.19

~o m~ 2.00 2.25 2.50 2.75 3.00 3.25

Page 1 of 100

~

I.S. RUN 01_Blank

1.29

J I 0.78

0.81 1.24 0.84 '

1.22

' 0.86

0.751. I\( 1.20

% 0.91 1.32

0.94

( 1.131 111.36 1.71 1.82

~o m~ f Ý O~ 1.00 1.~ 1.W 1.~ 2.00

47






Name: RUN 01_SO, Date: 24-Sep-2013, Time: 15:47:24, Vial: 1:2

OCT DG RUN 01_SO RUN 01_SO

1.80 2.27

90 90

2.88

3.01

% %

2.74

3.31

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_so

90

%

~

I.S. 1.86

1527273.88 0.79 ng/ml

Page 2of100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

}ř

48






Name: RUN 01_S8, Date: 24-Sep-2013, Time: 15:51:37, Vial: 1:3

OCT DG RUN 01_S8 RUN 01_S8

OCT DG 2.24

9J

2.41 l 1443.67 1453.41 0.13 0.12 ng/ml

90 i

% % 2.87

2.92

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 3of100

~

I.S. RUN 01_S8

I.S.

l 1.87 2017119.38 1.04 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

r

49


MassLynx 4.1 SCN 843

Data set: C:\MassLynx\CPA 430-13.PRO\RUN 01.qld




OCT DG RUN 01_87 RUN 01_87

DG

J '~ 1 1826.11 0.77 ng/ml ,

% %

2.84

2.94

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 4of100

~

I.S. RUN 01_87

I.S.

1 1.86 1697087.00 0.88 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00 r

50






Name: RUN 01_$6, Date: 24-Sep-2013, Time: 16:00:01, Vial: 1:5


DG

9J

2.42 l 3674.22 1.99 ng/ml

90 ~

% %

2.91

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 5of100

~

I.S. RUN 01_86

I.S.

l 1.87 2102592.50 1.09 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

/r

51






Name: RUN 01_85, Date: 24-Sep-2013, Time: 16:04:13, Vial: 1:6


DG

9J

2.43 l 8543.89 . 8.48 ng/ml

901

% %

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 6of100

~

I.S. RUN 01_85

I.S.

l 1.86 1583843.00 0.82 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

ff

52



Data set: C:\Masslynx\CPA 430-13.PRO\RUN 01.qld





OCT DG 2.25

9J

2.42 l 103855.64 41092.50 ·. :5.28 nglml 23.66 nglml

90 i

% %

~o m~ ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 7 of 100

~

I.S. RUN 01_84

I.S.

l 1.87 2830984.75 1.46 nglml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

ff

53







OCT DG RUN 01_S3 RUN 01_S3

DG

2.43 l 95170.95

77.30 ng/ml '· 901 90

% %

~o m~ ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 8of100

Á

I.S. RUN 01_S3

I.S.

l 1.87 1789783.75 0.93 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

ff

54




Last Altered: Tuesday, October 15, 2013 09:11 :13 Centra! Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Central Europe Daylight Time




DG

2.43 l 407290.00 258.19 ng/ml .

90 ~ 90

% %

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 9of100

~

I.S. RUN 01_82

I.S.

l 1.87 1580408.88 0.82 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

/I

55








OCT DG 2.26

9J

2« l 3649432.50 1161611.38 506.17 ng/ml 461.91 ng/ml

90 ~ -

% %

-10 min ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 10of100

~

I.S. RUN 01_81

I.S.

l 1.86 1858567.25 0.96 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

'

56






Name: RUN 01_QC3a, Date: 24-Sep-2013, Time: 16:25:17, Vial: 1:11

OCT DG RUN 01_QC3a RUN 01_QC3a

DG

242 ) 2054.96 0.34 ng/ml ..

90 i 90

% %

2.90

2.90

1.81

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 11 of 100

~

I.S. RUN 01_QC3a

I.S.

l 1.87 2436259.00 1.26 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

'

57







OCT DG RUN 01_101101 RUN 01 101101

1.81 2.93

90

2.88 3.26

2.28

% %

1.84 2.46

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_ 101101

90

%

~

I.S. 1.86

2012917.00 1.04 ng/ml

Page 12of100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

~

58



Dataset: C:\MassLynx\CPA 430-13.PRO\RUN 01.qld




OCT RUN 01_ 101102

1.95

90 2.26

2.89

%

-10 min 2.00 2.25 2.50 2.75 3.00 3.25

DG RUN 01_101102

90

%

DG 2.44

76922.24 47.97 ng/ml

~o m~ 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 101102

90

%

~

I.S. 1.86

2498240.75 1.29 ng/ml

Page 13of100

-10 min Qn 1.00 1.~ 1.~ 1.n 200

ff

59




Last Altered: Tuesday, October 15, 2013 09:11 :13 Central Europe Daylight Time Printed: At Tuesday, October 15, 2013 09: 12:04 Central Europe Daylight Time



OCT DG RUN 01_ 101201 RUN 01 101201

1.86 2.90

90 90 2.85

2.32

3.15

% % .1.81

2.47

~o m~ ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 101201

90

%

Ao

I.S. 1.86

2114568.50 1.09 ng/ml

Page 14 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

Ir

60







OCT DG RUN 01_ 101202 RUN 01_ 101202

2.94

90 90

% %

2.02

-10 min ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_ 101202

90

%

A

I.S. 1.87

2040328.38 1.06 ng/ml

Page 15 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

fr

61




Last Altered: Tuesday, October 15, 2013 09:11:13 Central Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Central Europe Daylight Time



OCT RUN 01_ 101301

1.83

90 2.81

2.32

% %

2.47

1.81

2.91

Page 16 of 100

~

%

3.42

-10 min -10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25 0.75 1.00 1.25 1.50 1.75 2.00

t

62







OCT DG RUN 01_101302 RUN 01_101302

1.80 DG

90

246 l 36336.61 28.44 ng/ml

901

2.74

2.42

3.01

% %

2.14

~o m~ ~o m~ 2.00 2.25 2.50 2. 75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 17of100

Á

I.S. RUN 01_ 101302

I.S.

l 1.86 2070223.50 1.07 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00 :r

63







OCT DG RUN 01_ 101401 RUN 01_ 101401

1.81 2.90

90 i I I

2.57

2.94

2.08 % %

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 18 of 100

~

I.S. RUN 01_101401

I.S. 1.87

1834925.13 0.95 ng/ml

90

%

~o m~ o.n 1.00 1.~ 1.~ 1.n ~oo

F

64




Last Altered: Tuesday, October 15, 2013 09:11 :13 Central Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Central Europe DaylightTime



OCT RUN 01_ 101402

1.83

90 2.27

2.93

1.81

% %

3.26

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 19 of 100

Á

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

fr

65







% %

1.81

2.43

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 20 of 100

~

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

/(

66







OCT DG RUN 01_ 101502 RUN 01_ 101502

1.81 DG

90

'~ ) 230950.30 143.16 ng/ml

90 4 2.41

2.92

% %

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 21 of 100

~

I.S. RUN 01 101502

I.S.

1 1.86 2018839.63 1.04 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f

67







OCT DG RUN 01_102101 RUN 01_ 102101

1.82 2.92

90 90

2.84

2.48

% % 1.96

-10 min ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_102101

90

%

Á

I.S. 1.86

1441221.50 0.75 ng/ml

Page 22 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f(

68







OCT DG RUN 01_102102 RUN 01 102102

1.81 2.25 DG

3.23 l 2.46 42232.16

31.42 90 i \ I I L.IV I \ 90 i ~

% %

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 23 of 100

~

I.S. RUN 01 102102

I.S.

l 1.87 2167449.50 1.12 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

rr

69



Data set: C:\MassLynx\CPA 430-13.PRO\RUN 01.qld

Last Altered: Tuesday, October 15, 2013 09:11 :13 Centra! Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Centra! Europe DaylightTime



OCT RUN 01_102201

1.61

90

% %

1.81

~o m~ ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 24 of 100

~

%

~o m~

0.75 1.00 1.25 1.50 1.75 2.00

ff

70



Dataset: C:\MassLynx\CPA 430-13.PRO\RUN 01.qld



Name: RUN 01_ 102202, Date: 24-Sep-2013, Time: 17:26:25, Vial: 1:25

OCT DG RUN 01_ 102202 RUN 01 102202

2.21 2.89

2.57 J A 1.81 I I ~ 90-ť

1.81

2.88

3.13

3.44

% %

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 25 of 100

~

I.S. RUN 01 102202

I.S.

l 1.87 3209653.50 1.66 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

/!

71




Last Altered: Tuesday, October 15, 2013 09:11 :13 Central Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Centra! Europe Daylight Time



OCT DG RUN 01_102301 RUN 01_102301

1.81 1.81

2.38

90 90

2.65 3.35

3.14 % %

2.09

2.61

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 102301

90

%

~

I.S. 1.87

2160598.00 1.12 ng/ml

Page 26 of 100

-10 min Q~ 1.00 1.~ 1.~ 1.~ 200

fr

72







OCT DG RUN 01_102302 RUN 01_ 102302

2.27 DG 1.81 (\ l

2.49 l 242840.34 158.11 ng/ml

90 i\ I \ 90 i

2.87

% %

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 27 of 100

Á

I.S. RUN 01_ 102302

I.S.

l 1.87 1862098.63 0.96 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

f(

73







OCT DG RUN 01_102401 RUN 01_102401

1.80 2.93

90 90

2.51

2.97

3.26

% 2.66 %

1.81

~o m~ ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 102401

90

%

~

I.S. 1.87

1524693.25 0.79 ng/ml

Page 28 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

fr

74






Name: RUN 01_QC2b, Date: 24-Sep-2013, Time: 17:43:15, Vial: 1:29

OCT DG RUN 01_QC2b RUN 01_QC2b

OCT DG 2.28

90, 2.46 )

1279975.88 490611.19 257.50 ng/ml 258.39 ng/ml .

90-l -

% %

-10 min ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 29 of 100

I.S. RUN 01_QC2b

I.S.

l 1.87 1901631.13 0.98 ng/ml

90

%

-10 min o. 75 1.00 1.25 1.50 1.75 2.00 r

75




Last Altered: Tuesday, October 15, 2013 09:11 :13 Central Europe DaylightTime Printed: At Tuesday, October 15, 2013 09:12:04 Central Europe Daylight Time



OCT DG RUN 01 102402 RUN 01_ 102402

2.95

90 90

% % '1.81

2.45

3.31

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_ 102402

90

%

I.S. 1.87

2215766.50 1.15 ng/ml

Page 30 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

fr

76




Last Altered: Tuesday, October 15, 2013 09:11: 13 Central Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Central Europe Daylight Time



2.81 3.28

% %

1.81

2.44

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 31 of 100

~

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

ff

77







OCT DG RUN 01 102502 RUN 01 102502

2.68 DG 2.52

94226.94 56.23

90-l I I 90-l

1.81

% % 2.86

3.00

~o m~ ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 32 of 100

I.S. RUN 01_102502

I.S.

l 1.87 2561494.25 1.33 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

f

78







OCT RUN 01_103101

1.80

90

2.77

% %

1.81 2.47 3.28

2.97

~o m~ ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 33 of 100

~

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f

79







OCT DG RUN 01_ 103102 RUN 01_ 103102

1.80 1.81

90

2.31

3.25 2.87

2.33

% % 2.51

2.65

3.26

3.14

·10 min ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 103102

90

%

~

I.S. 1.87

1555503.13 0.80 ng/ml

Page 34 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

r

80







OCT DG RUN 01 103201 RUN 01 103201

2.27 2.90

90 90

1.82

2.96

% %

1.81

2.48

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 103201

90

%

~

I.S. 1.87

2098456.25 1.09 ng/ml

Page 35 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

fí

81







OCT RUN 01_103202

1.81

90

2.34

2.92

%

-10 min 200 2~ 2W 2~ ~00 3~

DG RUN 01_103202

90

%

DG 2.52

167338.02 95.11 ng/ml

-10 min 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_103202

90

%

~

I.S. 1.87

2452423.75 1.27 ng/ml

Page 36 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

rr

82







OCT DG RUN 01_103301 RUN 01 103301

2.32 2.92

90 90 2.90

1.81

2.68

% %

1.81

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 103301

90

%

~

I.S. 1.87

1344906.63 0.70 ngfml

Page 37 of 100

~o m~

0.75 1.00 1.25 1.50 1.75 2.00

f(

83







OCT DG RUN 01_103302 RUN 01_103302

2.31 DG

,~ I 103439.49 60.72 ng/ml

90 i I I 90 i

1.81

2.82

% %

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 38 of 100

I.S. RUN 01_103302

I.S.

l 1.87 2576213.75 1.33 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

fr

84







OCT DG RUN 01_103401 RUN 01 103401

2.32 2.92

1.81

90 90

2.91

2.56

% %

1.81

2.15

-10 min -10 min 2.00 2.25 2.50 2. 75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 103401

90

%

~

I.S. 1.87

2170881.50 1.12ng/ml

Page 39 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

85







OCT RUN 01_103402

90

%

OCT 2.32

44780.83 14.71 ng/ml

-10 min 2.00 2.25 2.50 2. 75 3.00 3.25

DG RUN 01_103402

2.94

90

2.58

%

1.81

~o m~ 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_103402

90

%

~

I.S. 1.87

2154266.50 1.11 ng/ml

Page 40 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f(

86







OCT RUN 01_103501

2.82

90

2.47

2.00

3.29

3.03

% %

1.81

~o m~ ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

%

tJ ~

Page 41 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

ť

87







OCT RUN 01_ 103502

1.81

90

2.29

2.93

%

-10 min 2.00 2.25 2.50 2.75 3.00 3.25

DG RUN 01_ 103502

90

%

DG 2.53

32807.79 19.69 ng/ml

-10 min 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_ 103502

90

%

~

I.S. 1.87

2722625.25 1.41 ng/ml

Page 42 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

f(

88







OCT DG RUN 01 104101 RUN 01_ 104101

1.81 2.17 2.93

2.90 90 90

3.13 3.35

% %

1.81

-10 min ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_104101

90

%

~

I.& 1.~

179771a13 o.m~ml

Page 43 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

rr

89







OCT DG RUN 01_104102 RUN 01_104102

1.81 DG

2.54 l 165169.70 107.10 ng/ml

2.89 90 ~

3.22

% %

-10 min ~o m~ 2.00 2.25 2.50 2. 75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 44 of 100

A

I.S. RUN 01 104102

I.S.

l 1.87 2090878.13 1.08 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

r

90




La st Altered: Tuesday, October 15, 2013 09: 11: 13 Central Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Central Europe Daylight Time



OCT DG RUN 01_104201 RUN 01_ 104201

1.81 2.89

2.28 90 ~ I I 90 i \ I\

2.90

2.55

% %

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 45 of 100

Á

I.S. RUN 01 104201

I.S. 1.87

1569367.38 I 0.81 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f

91







OCT DG RUN 01_ 104202 RUN 01_ 104202

2.93

90 90

% %

1.81

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 104202

90

%

rť,

I.S. 1.87

2289054.25 1.18 ng/ml

Page 46 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

'

92






Name: RUN 01_QC1c, Date: 24-Sep-2013, Time: 18:58:57, Vial: 1:47

OCT DG RUN 01_QC1c RUN 01_QC1c

OCT DG

'·" A 9J

2.56 l 2369405.75 833645.00 394.30 ng/ml 379.62 ng/ml

90-I

% %

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 4 7 of 100

I.S. RUN 01_QC1c

I.S.

l 1.87 1815497.63 0.94 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

93







OCT DG RUN 01_104301 RUN 01_ 104301

1.81 2.89

901 I I

2.37

1.81

%

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 48 of 1 00

I.S. RUN 01 104301

I.S. 1.87

2392956.75 1.24 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

fr

94

Quantify Sample Report CPA_ 430_13






OCT DG RUN 01_ 104302 RUN 01 104302

2.29 DG 1.81 A.

2.85 l 2.53 78559.66

73.22 901 \ I '..... I \ 90 i

3.32

% %

-10 min ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 49 of 1 00

~

I.S. RUN 01 104302

I.S.

l 1.87 1575061.50 0.82 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

rr

95







OCT DG RUN 01_ 104401 RUN 01_ 104401

1.81 2.30 2.90

3.12 90 ~ I \ 901 \ I \ /\

% %

1.81

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 50 of 100

~

I.S. RUN 01 104401

I.S. 1.87

1838068.00 I 0.95 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

96







OCT DG RUN 01_ 104402 RUN 01 104402

1.81 2.29 2.92

90 90 2.98

% % 2.53

1.81

-10 min ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 104402

90

%

~

I.S. 1.87

1690902.88 0.87 ng/ml

Page 51 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

r

97







OCT DG RUN 01_104501 RUN 01_ 104501

1.81 2.90

90 i I I

2.90 2.11

% %

-10 min ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 52 of 100

Á

I.S. RUN 01 104501

I.S. 1.86

1918706.50 0.99 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

98







OCT RUN 01_ 104502

1.82

90

2.87

%

-10 min 2.00 2.25 2.50 2. 75 3.00 3.25

DG RUN 01_ 104502

90

%

DG 2.53

31697.41 27.48 ng/ml

2.05

-10 min 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 104502

90

%

~

I.S. 1.86

1872049.63 0.97 ng/ml

Page 53 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

(

99







OCT DG RUN 01_105101 RUN 01_ 105101

1.81 2.94

90 90

2.90

% %

1.81 2.66

-10 min ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 105101

90

%

h /7 „~

I.S. 1.86

1529741.25 0.79 ng/ml

Page 54 of 1 00

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

f

100







OCT DG RUN 01_105102 RUN 01_105102

2.84 DG

2.53 ) 66422.27 88.22 ng/ml

90 i I I I 90 i

2.00

% %

2.05

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 55 of 100

~

I.S. RUN 01_105102

I.S.

l 1.86 1066569.13 0.55 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

r

101




LastAltered: Tuesday, October 15, 2013 09:11:13 Central Europe DaylightTime Printed: At Tuesday, October 15, 2013 09: 12:04 Centra I Europe Daylight Time


Name: RUN 01_105101REPE, Date: 24-Sep-2013, Time: 19:36:52, Vial: 2:8

OCT DG RUN 01_105101REPE RUN 01_105101REPE

2.95

90 90

1.81

% %

1.81

2.34

·10 min -10 min 2.00 2.25 2.50 2. 75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 105101REPE

90

%

Á

I.S. 1.84

1434943.75 0.74 ng/ml

Page 56 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

fr

102

Quantify Sample Report CPA_ 430_13






OCT RUN 01_105102REPE

90

1.83

2.91

%

-10 min 2.00 2.25 2.50 2.75 3.00 3.25

DG RUN 01_105102REPE

90

%

2.00

DG 2.53

86275.59 81.01 ng/ml

~o m~

2.00 2.25 2.50 2.75 3.00 3.25


90

o/o

~

I.S. 1.86

1534557.88 0.79 ng/ml

Page 57 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

t

103







OCT DG RUN 01_105201 RUN 01_105201

1.81 2.89

90 901 I \

1.97

2.87 2.40

%

2.37

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 58 of 100

~

I.S. RUN 01 105201

I.S. 1.86

1539134.00 0.80 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

rr

104




Last Altered: Tuesday, October 15, 2013 09: 11: 13 Central Europe Daylight Time Printed: At Tuesday, October 15, 2013 09: 12:04 Central Europe Daylight Time



OCT DG RUN 01_105202 RUN 01_105202

2.92

90 90

2.87

1.81

2.26 2.51

% %

1.84

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_105202

90

%

Á

I.S. 1.86

1167856.38 0.60 ng/ml

Page 59 of 100

-10 min ~n 1.00 1~ 1.~ 1.n 200

fr

105




Last Altered: Tuesday, October 15, 2013 09:11: 13 Centra I Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Central Europe Daylight Time



OCT DG RUN 01_ 105301 RUN 01_ 105301

1.81 2.86

2.55 901 I I

3.00

% %

1.81

~o m~ ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 60 of 100

I.S. RUN 01 105301

I.S. 1.86

1709660.75 0.88 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

106







OCT DG RUN 01_ 105302 RUN 01_105302

1.81 DG

2.84 --,

2~ l 154152.13 130.55 ng/ml

90-l \ I I / 90-l

% %

-10 min ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 61 of 100

I.S. RUN 01 105302

I.S.

l 1.86 1518659.75 0.79 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

107







OCT DG RUN 01_ 105401 RUN 01_ 105401

2.91 2.90

90 90 l I \ 3.17

1.81

2.56

% %

1.96

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 62 of 1 00

A

I.S. RUN 01 105401

I.S. 1.86

1764998.88 0.91 ng/mL

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

108







OCT RUN 01_105402

90

% %

1.81

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 63 of 100

Jo

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

rr

109







OCT RUN 01_ 105501

2.07

90

2.84

2.48

% %

2.15

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 64 of 100

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

rr

110




Last Altered: Tuesday, October 15, 2013 09:11 :13 Centra! Europe Daylight Time Printed: At Tuesday, October 15, 2013 09: 12:04 Centra I Europe Daylight Time


Name: RUN 01_QC3d, Date: 24-Sep-2013, Time: 20:14:47, Vial: 2:17

OCT DG RUN 01_QC3d RUN 01_QC3d

OCT DG

2.36 l J 2~ 1 2456.29 1986.40 0.36 ng/ml 0.31 ng/ml

90,

% %

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 65 of 100

~

I.S. RUN 01_QC3d

I.S.

l 1.87 2403880.75 1.24 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

'

111







OCT RUN 01_ 105502

90

2.89

1.81

%

~o m~ 2.00 2.25 2.50 2.75 3.00 3.25

DG RUN 01_105502

90

%

DG 2.53

41132.23 55.29 ng/ml

~o m~ 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_105502

90

%

~

I.S. 1.86

1139683.50 0.59 ng/ml

Page 66 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

ff

112







OCT DG RUN 01_ 106101 RUN 01_ 106101

1.81 2.87

90 901 I I

2.87

2.34

% %

1.81

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 67 of 100

~

I.S. RUN 01 106101

I.S. 1.86

1738780.13 0.90 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

ff

113




Last Altered: Tuesday, October 15, 2013 09:11 :13 Central Europe Daylight Time Printed: At Tuesday, October 15, 2013 09: 12:04 Centra I Europe Daylight Time



OCT DG RUN 01_106102 RUN 01_106102

2.90

90 90-I I I

% % 11.81

-10 min ~o rn~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 68 of 100

d

I.S. RUN 01_106102

I.S. 1.86

1756368.50 0.91 ng/rnl

90

%

~o rn~ 0.75 1.00 1.25 1.50 1.75 2.00

r

114







OCT DG RUN 01_ 106201 RUN 01_ 106201

1.92 2.89

90 90

3.23

2.47 2.83

% %

1.81

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_ 106201

90

%

I.S. 1.86

1512339.00 0.78 ng/ml

Page 69 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

fr

115







OCT DG RUN 01 106202 RUN 01 106202

DG

90

2.48 ) 42327.29 39.72 ng/ml ·

901

1.81 2.97

2.07

% %

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 200 2~ 2w 2n aoo a~

Page 70 of 100

I.S. RUN 01_ 106202

I.S.

l 1.86 1690854.88 0.87 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00 ,

116




Last Altered: Tuesday, October 15, 2013 09:11 :13 Centra! Europe Daylight Time Printed: At Tuesday, October 15, 2013 09: 12:04 Centra! Europe Daylight Time



2.87

% %

1.81

2.12

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 71 of 100

~

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

/(

117







OCT RUN 01_106302

1.81

90

2.89

%

-10 min 2.00 2.25 2.50 2. 75 3.00 3.25

DG RUN 01_106302

90

%

DG 2.54

76785.72 68.98 ng/ml

~o m~ 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_106302

90

%

~

I.S. 1.86

1650710.38 0.85 ng/ml

Page 72 of 1 00

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

ff

118







ocr DG RUN 01_ 106401 RUN 01_ 106401

1.81 2.89

901 I I

1.81

% 2.45

3.04

·10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 73 of 100

Á

I.S. RUN 01 106401

I.S. 1.86

2246457.25 1.16 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f

119







OCT DG RUN 01_106402 RUN 01 106402

1.81 2.94

90 90

2.53 2.89

% % 1.81

-10 min ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2. 75 3.00 3.25

I.S. RUN 01 106402

90

%

~

I.S. 1.86

1831558.13 0.95 ng/ml

Page 74of100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

120







OCT DG RUN 01_106501 RUN 01 106501

1.81 2.90

2.87 90 90

2.49

% %

1.81

2.26

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

~

I.S. RUN 01_ 106501

90

%

I.S. 1.87

1805932.13 0.93 ng/ml

Page 75 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00 ,

121







OCT DG RUN 01_106502 RUN 01 106502

1.81 DG ~

2.50 l 182493.34 128.23 ng/ml

90 i \ 2.89 I 90 i

% %

1.97

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 76 of 100

I.S. RUN 01 106502

I.S.

l 1.86 1839884.00 0.95 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

ff

122







3.26

2.94

%

2.57

1.81

-10 min ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 77 of 100

Á

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f

123







OCT DG RUN 01_ 107102 RUN 01_107102

1.81 DG

,~ I 53735.31 73.15 ng/ml

901

2.69

1.97

3.17

% %

-10 min ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 78 of 100

~

I.S. RUN 01_ 107102

I.S.

l 1.84 1078416.63 0.56 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f

124




Last Altered: Tuesday, October 15, 2013 09:11:13 Centra! Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Centra! Europe Daylight Time



OCT DG RUN 01_107101REPE RUN 01_107101REPE

1.81 2.93

90 90

2.41

3.03

1.81

o/o o/o

~o m~ ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Á


90

o/o

I.S. 1.84

1795434.38 0.93 ng/ml

Page 79 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f

125







OCT DG RUN 01_ 107102REPE RUN 01_107102REPE

1.81 2.90 DG A --,

2.52 l 252994.58

90 i \ 154.45 ng/ml

I \ 90-l

2.25

2.57

% %

1.96

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 80 of 100

~

I.S. RUN 01_ 107102REPE

I.S.

l 1.86 2001187.13 1.04 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f

126




Last Altered: Tuesday, October 15, 2013 09:11:13 Centra! Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Centra! Europe Daylight Time



OCT DG RUN 01_ 107201 RUN 01 107201

1.82 2.92 2.89

90 90

2.59

2.21

% %

1.81

~o m~ ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_107201

90

%

A

I.S. 1.84

1256443.38 0.65 ng/ml

Page 81 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

f

127







OCT RUN 01 107202

1.81

90

2.91

% %

1.81

-10 min ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 82 of 100

A

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

fř

128






Name: RUN 01_QC2e, Date: 24-Sep-2013, Time: 21:30:29, Vial: 2:35

OCT DG RUN 01_QC2e RUN 01_QC2e

DG

2.45 1 461764.94 253.51 ng/ml

901 90

%

~o m~ ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 83 of 1 00

~

I.S. RUN 01_QC2e

I.S.

l 1.86 1839907.50 0.95 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

r

129







OCT DG RUN 01_107301 RUN 01_ 107301

2.88

90 90 1.95

3.06

2.42

% %

1.81

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_ 107301

90

%

~

I.S. 1.83

1132307.38 0.59 ng/ml

Page 84 of 100

~o m~ QH 1.00 1~ 1.W 1.H 2.00

fř

130







OCT DG RUN 01_107302 RUN 01_107302

3.11 DG

90

2.46 l 31509.47 34.39 ng/ml

90 ~

2.48

% %

~o m~ ~o m~ 2.00 2.25 2.50 2. 75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 85 of 1 00

~

I.S. RUN 01 107302

I.S.

l 1.76 1469642.63 0.76 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

'

131







OCT DG RUN 01_107401 RUN 01_ 107401

2.92

2.93 90 -11.81 90

2.29

o/o o/o

1.81

3.34

~o m~ ~o m~ 2.00 2.25 2.50 2. 75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 107401

90

o/o

I.S. 1.86

1381822.00 0.72 ng/ml

Page 86 of 1 00

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

132




Last Altered: Tuesday, October 15, 2013 09:11 :13 Centra! Europe Daylight Time Printed: At Tuesday, October 15, 2013 09: 12:04 Central Europe Daylight Time



OCT RUN 01_107402

90

% %

2.11

~o m~ ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 87 of 100

~

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

f

133







OCT DG RUN 01_107501 RUN 01_107501

2.94

90 90

2.10 1.81

2.58

% %

-10 min ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_ 107501

90

%

Á

I.S. 1.76

1252990.75 0.65 ng/ml

Page 88 of 100

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

134







OCT RUN 01 107502

3.01 2.50

90

1.81

%

DG RUN 01_ 107502

90

%

1.81

DG 2.54

56112.38 68.07 ng/ml

3.22

-10 min ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 107502

90

%

~

I.S. 1.83

1225055.88 0.63 ng/ml

Page 89 of 100

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

ť

135







OCT DG RUN 01 108101 RUN 01_ 108101

2.88

90 90-l I I

2.10 1.81

%

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 90 of 100

Á

I.S. RUN 01_ 108101

I.S. 1.86

1465095.88 0.76 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

f

136







OCT DG RUN 01_108102 RUN 01_108102

2.89 DG

2.53 ) 34630.37 32.82 ng/ml

901 I \ 901

1.81

% %

2.08

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 91 of 100

~

I.S. RUN 01 108102

I.S.

l 1.84 1697370.38 0.88 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

137







OCT DG RUN 01_108201 RUN 01_108201

1.81 2.90 2.88

90 i - \ I I 90 i I I

% %

1.81

2.22

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 92 of 100

~

I.S. RUN 01_ 108201

I.S. 1.86

1759233.00 0.91 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

r

138




Last Altered: Tuesday, October 15, 2013 09:11: 13 Centra I Europe Daylight Time Printed: At Tuesday, October 15, 2013 09:12:04 Central Europe Daylight Time



OCT DG RUN 01 108202 RUN 01_108202

2.88

90 i 9J (\

% %

1.81

1.81

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 93 of 1 00

4

I.S. RUN 01_ 108202

I.S.

l 1.86 1605532.25 0.83 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f

139







OCT DG RUN 01_ 108301 RUN 01_108301

1.95 2.88

2.71 90 ~ I I 90 ~ \ (\

% %

1.81

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 94 of 100

~

I.S. RUN 01_108301

I.S. 1.86

1133263.63 I 0.59 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

f

140







ocr DG RUN 01_ 108302 RUN 01_ 108302

1.81 DG

2.53 l 69319.82 79.05 ng/ml

90 ~

%

1.93

~o m~ ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 95 of 100

~

I.S. RUN 01 108302

I.S.

l 1.86 1269405.00 0.66 ng/ml

90

%

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

fr

141







OCT RUN 01_ 108401

90

2.90

% % 1.81

1.81

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 96 of 100

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

ff

142







3.03

% %

1.81 2.40

~o m~ -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 97 of 100

~

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

fY

143







OCT DG RUN 01_ 108501 RUN 01_ 108501

1.89 2.94

90

3.09

2.31

3.26

% %

1.81

2.44

-10 min -10 min 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01 108501

90

%

~

I.S. 1.87

1977807.50 1.02 ng/ml

Page 98 of 1 00

~o m~ 0.75 1.00 1.25 1.50 1.75 2.00

r

144







OCT DG RUN 01_108502 RUN 01_108502

2.71

2.03

90 90 3.17

2.59 3.39

% %

-10 min ~o m~

2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

I.S. RUN 01_108502

90

%

Á

I.S. 1.87

1918168.38 0.99 ng/ml

Page 99 of 100

~o m~ 0.75 1.00 1.25 1.50 1. 75 2.00

r

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Name: RUN 01_QC1f, Date: 24-Sep-2013, Time: 22:41:53, Vial: 1:18

OCT DG RUN 01_QC1f RUN 01_QC1f

OCT DG

2$ l J 2.69 A 3157089.25 994332.81 430.40 ng/ml 387.26 ng/ml .

90-l

% %

~o m~ ~o m~ 2.00 2.25 2.50 2.75 3.00 3.25 2.00 2.25 2.50 2.75 3.00 3.25

Page 100 of 100

~

I.S. RUN 01_QC1f

I.S.

l 1.86 2099649.25 1.09 ng/ml

90

%

-10 min 0.75 1.00 1.25 1.50 1.75 2.00

(

146

Bioanalytical Report - server webhostingu Savana.cz · 2016-08-25 · To the best oj my knowledge,...

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Transcript of Bioanalytical Report - server webhostingu Savana.cz · 2016-08-25 · To the best oj my knowledge,...