it’s the same but different - roche · it’s the same but different roche methadone metabolite...

It’s the same but different

Roche Methadone Metabolite qualitative assay vs

Roche Methadone Metabolite semiquantitative assay

Christian

Biochemistry Department – SCL Dunedin

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.

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

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.

Methadone toxicity

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.

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.

Methadone measurement

Methadone measurement is critical for

methadone compliance monitoring.

Parent drug (methadone) vs Methadone

metabolite (EDDP)

GC/LC-MS vs Immunoassay.

Roche Methadone Metabolite assays

MM1Q – Qualitative assay (100 ng/mL)


MM1S – Semiquantitative assay (100 ng/mL)

MM3S – Semiquantitative assay (300 ng/mL)

Roche Methadone Metabolite assay principle

In the presence of EDDP

Roche Methadone Metabolite assay principle

In the presence of EDDP In the absence of EDDP

Measuring methadone metabolite at SCL Dunedin


Calibrator: DRI Methadone Metabolite Calibrator 100

Quality controls:

DRI Methadone Metabolite Negative Control 75 ng/mL

DRI Methadone Metabolite Positive Control 125 ng/mL

MM1Q QC ProblemMMNeg and MMPos

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

More MM1Q QC problem (our own doing)In-house Positive MM QC

More MM1Q QC problem (our own doing)In-house Negative MM QC

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

Roche Methadone Metabolite semiquantitative assay (100 ng/mL)

Calibrators:

DRI Methadone Metabolite Calibrator 0





Quality controls:

DRI Methadone Metabolite Negative Control 75 ng/mL

DRI Methadone Metabolite Positive Control 125 ng/mL

MM1S QC performanceMMNeg and MMPos

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

Specificity and sensitivity

MM1Q

Negative

MM1Q

Positive

MM1S

Negative21 0

MM1S

Positive0 21

Specificity : 100%

Sensitivity: 100%

Discussion

Is MM1Q a good assay compared to MM1S?

Is MM1Q a reliable assay compared to MM1S?

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.

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

What did happen to Claire?

Claire had been working on the same floor for 46 years!!!

it’s the same but different - roche · it’s the same but different roche methadone metabolite...

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