It’s the same but different - Roche · It’s the same but different Roche Methadone Metabolite...
Transcript of It’s the same but different - Roche · It’s the same but different Roche Methadone Metabolite...
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It’s the same but different
Roche Methadone Metabolite qualitative assay vs
Roche Methadone Metabolite semiquantitative assay
Christian
Biochemistry Department – SCL Dunedin
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Methadone
Methadone is a synthetic opiates and a derivative of diphenylpropylamine.
It’s also known as Dolophine, Methadose, Physeptone, Eptadone, Mephenon, Metasedin, and Symoron.
It’s mainly used for analgesia and in the treatment of opioid addiction.
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The use of methadone
In 1965, methadone was introduced for the treatment of heroin addiction.
It’s thought to have oral effectiveness, moderately long-lasting effect, and milder withdrawal.
After initial stabilisation, the full treatment dose is typically 80-120 mg/day.
Methadone vs Buprenorphine
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Methadone toxicity
Methadone is New Zealand’s fifth most dispensed drug (1.85 million doses in 2016).
There are approximately 5500 people on methadone treatment in New Zealand.
The d-form avidly binds to the hERG potassium receptor and may cause sudden death.
High risk for individuals with polymorphic for CYP2B6.
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Methadone toxicity
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Methadone toxicity
Methadone is New Zealand’s fifth most dispensed drug (1.85 million doses in 2016).
There are approximately 5500 people on methadone treatment in New Zealand.
The d-form avidly binds to the hERG potassium receptor and may cause sudden death.
High risk for individuals with polymorphic for CYP2B6.
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Methadone metabolism
Hydroxylation and glucuronidation occur but approximately 75% of the drug remains unconjugated and as much as 33% of the drug may be excreted within 24 hours in the urine.
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Methadone measurement
Methadone measurement is critical for
methadone compliance monitoring.
Parent drug (methadone) vs Methadone
metabolite (EDDP)
GC/LC-MS vs Immunoassay.
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Roche Methadone Metabolite assays
MM1Q – Qualitative assay (100 ng/mL)
MM3Q – Qualitative assay (300 ng/mL)
MM1S – Semiquantitative assay (100 ng/mL)
MM3S – Semiquantitative assay (300 ng/mL)
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Roche Methadone Metabolite assay principle
In the presence of EDDP
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Roche Methadone Metabolite assay principle
In the presence of EDDP In the absence of EDDP
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Measuring methadone metabolite at SCL Dunedin
MM1Q – Qualitative assay (100 ng/mL)
Calibrator: DRI Methadone Metabolite Calibrator 100
Quality controls:
DRI Methadone Metabolite Negative Control 75 ng/mL
DRI Methadone Metabolite Positive Control 125 ng/mL
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MM1Q QC ProblemMMNeg and MMPos
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MM1Q QC ProblemMMNeg and MMPos
QC Target Mean SD CV (%)
MMNeg 75 87.4 3.8 4.4
MMPos 125 120.2 3.5 2.9
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More MM1Q QC problem (our own doing)In-house Positive MM QC
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More MM1Q QC problem (our own doing)In-house Negative MM QC
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More MM1Q QC problem (our own doing)In-house Negative/Positive MM QC
In-house MM QC Target Mean SD CV (%)
Negative 0 3 6 227
Positive 168 167.8 20.6 12.3
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Roche Methadone Metabolite semiquantitative assay (100 ng/mL)
Calibrators:
DRI Methadone Metabolite Calibrator 0
DRI Methadone Metabolite Calibrator 100
DRI Methadone Metabolite Calibrator 300
DRI Methadone Metabolite Calibrator 500
DRI Methadone Metabolite Calibrator 1000
Quality controls:
DRI Methadone Metabolite Negative Control 75 ng/mL
DRI Methadone Metabolite Positive Control 125 ng/mL
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MM1S QC performanceMMNeg and MMPos
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MM1S QC performanceMMNeg and MMPos
QC Target Mean SD CV (%)
MMNeg 75 77.7 4.2 5.4
MMPos 125 129.1 4.7 3.7
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Specificity and sensitivity
MM1Q
Negative
MM1Q
Positive
MM1S
Negative21 0
MM1S
Positive0 21
Specificity : 100%
Sensitivity: 100%
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Discussion
Is MM1Q a good assay compared to MM1S?
Is MM1Q a reliable assay compared to MM1S?
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Conclusion
The QC performance of qualitative assays such
as MM1Q cannot be assessed statistically.
The comparison study shows that MM1Q assay is
as reliable as MM1S assay with100% sensitivity
and specificity.
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References
1. Methadone metabolite V7 [package insert]. Roche Diagnostics, Indianapolis, IN,
2016.
2. Karch SB, Drummer OH. Karch’s pathology of drug abuse. 5th Ed. CRC Press, Florida,
2016: 528-541.
3. Levine B. Principles of forensic toxicology. 3rd ED. AACC Press, Washington, 2009: 238-
239.
4. Langman L, Bechtel L, Holstegg CP. Clinical toxicology. In: Burtis CA, et al. Tietz
textbook of clinical chemisty & molecular diagnostics. 5th Ed. Elsevier, Missouri, 2012:
1144-1151.
5. Methadone fifth-most dispensed drug as patients describe hellish 'liquid handcuffs‘.
Stuff, New Zealand, 2016. http://www.stuff.co.nz/national/89874477/methadone-fifth-
most-dispensed-drug-as-patients-describe-hellish-liquid-handcuffs
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What did happen to Claire?
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Claire had been working on the same floor for 46 years!!!