PCA on pre-processed (2nd derivative + MSC) spectra (1085 – 1601 nm)

Identification of falsified antimalarial drugs using an innovative low cost portable

near infrared spectrophotometer

Analyzed samples

Moussa Yabré1, 2, *, Abdoul Karim Sakira2, Ludivine Ferey1, Pierre-Yves Sacré3, Roland D. Marini3, Karen Gaudin1, Issa T. Somé2

1 ChemBioPharm - ARNA INSERM U1212 / UMR CNRS 5320, Université de Bordeaux, France2 Laboratoire du développement du médicament, Université Joseph Ki-Zerbo, Burkina Faso

3 Laboratoire de Chimie Analytique, Département de Pharmacie, CIRM, Université de Liège, Belgique

* moussa.yabre@u-bordeaux.fr ; moussa.yabre@yahoo.fr

Thanks

INTRODUCTION

The phenomenon of substandard and falsified drugs becomes a serious threat topublic health in the worldwide, particularly in developing countries where drugsmonitoring and quality control (QC) systems are not very efficient. The occurrence offake medicines increases therapeutic failure, morbidity and mortality and the risk oftreatment resistance.

[1] Kovacs S, Hawes SE, Maley SN, Mosites E, Wong L, Stergachis A. Technologies for Detecting Falsified andSubstandard Drugs in Low and Middle-Income Countries. PLoS ONE, 9(3):e90601, 2014.[2] Dégardin K, Guillemain A, Guerreiro NV, Roggo Y. Near infrared spectroscopy for counterfeit detection using alarge database of pharmaceutical tablets. Journal of Pharmaceutical and Biomedical Analysis, 128:89-97, 2016.[3] Ciza PH, Sacre P-Y, Waffo C, Coïc L, Avohou H, Mbinze JK, Ngono R, Marini RD, Hubert Ph, Ziemons E. Comparingthe qualitative performances of handheld NIR and Raman spectrophotometers for the detection of falsifiedpharmaceutical products. Talanta, 202:469-78, 2019.

References Second and quantitative QC of all samples by HPLC or HPTLC to

identify substandard drugs Evaluation of the handheld device ability to detect substandard drugs Collection of more samples to build DD-SIMCA models for each

brand name Use of DD-SIMCA models built in routine analysis

Perspectives

NIR-S-G1(spectral range: 900-1700 nm)

Data Driven (DD)-SIMCA Classification

API Brand name Dosage (mg) Sales channel Designation Test batchesAL Dispersible S.Kant 20/120 Licite AL 20/120 dispersible S. Kant 1AL Ipca 20/120 Licite AL Ipca 2AL Macleods 20/120 Licite AL Macleods 5AL S.Kant 80/480 Licite AL 80/480 S. Kant 3AL Artefan 20/120 Licite Artefan 20/120 1AL Artefan 40/240 Licite Artefan 40/240 1AL Artefan 60/360 Licite Artefan 60/360 1AL Artefan 80/480 Licite Artefan 80/480 1AL Artefan Dispersible 20/120 Licite Artefan 20/120 dispersible 3

API Brand name Dosage (mg) Sales channel Designation Test batchesAL Coartem 20/120 Illicite Coartem 20/120 illicite channel 2AL Coartem 80/480 Licite Coartem 80/480 licite channel 1AL Colart 20/120 Licite Colart 1AL Combiart 80/480 Licite Combiart 80/480 licite channel 1AL Combiart 20/120 Licite Combiart 20/120 licite channel 7AL Combiart 20/120 Illicite Combiart 20/120 illicite channel 3AL Falciart 80/480 Licite Falciart 1AL Komefan 20/120 Licite Komefan 5AL R-Lume 80/480 Licite R-Lume 1

API Brand name Dosage (mg) Sales channel Designation Test batchesDP Duocotecxin 40/320 Licite Duocotecxin 6DP Ridmal 40/320 Licite Ridmal 2DP Malacur 40/320 Licite Malacur 2SP Maloxine 500/25 Licite Maloxine licite channel 5SP Maloxine 500/25 Illicite Maloxine illicite channel 3SP Combimal 500/25 Licite Combimal 2SP Laridox 500/25 Licite Laridox 2SP Fansidar 500/25 Licite Fansidar 2SP SP Strides Arcolab 500/25 Licite SP Strides Arcolab 1

SP

AL

DP

Atypic samples

Coartem and combiart samples boughtin illicite sale channel are falsified

without declared API

One of Duocotecxin batch is falsified without declared API

Maloxine samples from illicite sale channel are falsified withoutdeclared API

PCA on all AL DP SP data

PCA on all DP data

PCA on all SP data

PCA on all AL data

AL pre-processed mean spectra

Test of ability to identify a brand name

Genuine samples• AL : Combiart• DP : Duocotecxin• SP : Maloxine

Calibration set : at least 3 batches

Validation set : at least 2 independant batches

20 spectra per batch

In this study, we evaluated the potential of a low costhandheld NIR spectrophotometer (NIR-S-G1) in theidentification of falsified drugs of different antimalarialtablets:

The potential of spectroscopy techniques such as near infrared (NIR) and Ramanassociated to chemometric methods in the detection of substandard and falsifieddrugs are well known [1,2]. Also, these techniques have the advantages of being non-destructive, fast, requiring little or no sample preparation, as well as beingenvironmental friendly. However, the high cost of instruments classicallycommercialized limits their use in developing countries. Recently, some innovativehandheld and low cost NIR spectrophotometers (< 1000 €) have appeared on themarket. Besides their low cost, these portable devices can offer promisingperformance comparable to bench-top instruments [3].

DP pre-processed mean spectra

SP pre-processed mean spectra

Samples were collected in BurkinaFaso mainly in rural and border areas.

artemether/lumefantrine (AL)

dihydroartemisinin/piperaquine (DP)

sulfadoxine/pyrimethamine (SP)

FalsifiedCoartemCombiart

reference methodTLC from Minilab ®

Dimensions: 82 x 63 x 40 mmWeight: ~ 136 g

FalsifiedDuocotecxin

FalsifiedMaloxine

CombiartTP : 1FP : 0TN :1FN : 0

DuocotecxinTP : 1FP : 0TN :1FN : 0

MaloxineTP : 1FP : 0TN :1FN : 0

Correct identification of each brand name

FalsifiedCoartemCombiart

FalsifiedDuocotecxin

FalsifiedMaloxine