Hi Steve
Methadone is prescribed on a chronic bases hence both methadone and EDDP are at steady state. Therefore, both should be positive in urine.
I have seen often seen Methadone Pos and EDDP Neg, it's clearly a case of in-vitro addition of methadone.
The following scenarios are possible:
Urine Negative for methadone but Positive for EDDP:
- Check urine pH: most likely over 7.5 (methadone is reabsorbed at high urine pH). Investigate reason for elevated pH.
Urine Positive for methadone but Negative for EDDP
- Consider sample tampering: Methadone added post-void to the urine sample.
The following are potential reasons for change in urinary EDDP concentration:
- Change in methadone dose;
- Non-adherence to methadone dose;
- In vivo dilution;
- Change in co-medication that alters the half-life of methadone due to drug-drug interactions. [Kapur et. al. Methadone: A Review of drug-drug and pathophysiological interactions, Crit Rev Clin Lab Sci, 2011(Aug), 48(4): 171-195.].
For graph of EDDP elimination see Kapur et al. Pharmacogenetics of chronic Pain Management, Clinical Biochemistry, (2014) 47:1169-87.
bhushan
Dr. Bhushan M. Kapur, D.Phil, C.Chem, FRSC, FACB, FCACB
Associate Professor, Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto
"But today he saw one of the river's secret, one that gripped his soul.
He saw that the river continually flowed and flowed yet it was always there;
it was always the same and yet every moment it was new"
- Hermann Hesse in Siddhartha
-----Original Message-----
From: Clinical biochemistry discussion list [mailto:[log in to unmask]] On Behalf Of ACB-CLIN-CHEM-GEN automatic digest system
Sent: Friday, June 26, 2015 7:00 PM
Topics of the day:
4. EDDP-negative, methadone positive urines (2)
------------------------------
Date: Fri, 26 Jun 2015 15:40:31 -0400
From: Chesinta <[log in to unmask]>
Subject: Re: EDDP-negative, methadone positive urines
Hi Steve,
Multiple cytochromes metabolize methadone, before concluding on adulteration, have you considered any recent drug changes in the concerned patients ?
For example, drugs that induce CYP2B6 also induce methadone metabolism, and CYP 2B6 , of all the cytochromes has been shown to have the highest Vmax and lowest Km.
Is there more information you can provide ?
Thank you
Chesie Voma, PhD
University of Louisville
Clinical Chemistry Fellow
Sent from my Verizon Wireless 4G LTE Tablet
On Jun 22, 2015 10:40 AM, Steve Davis <[log in to unmask]> wrote:
>
> We have recently changed from a urine methadone to urine EDDP assay (both on a Roche c501) and have received enquiries from the clinical users of our service who are seeing patients negative for EDDP but who were reliably positive for methadone in the past. Our local referral lab has confirmed absence of EDDP & presence of methadone in these samples (by GC-MS), commenting that sample adulteration seems likely.
>
> There is some discussion on whether clients may be spiking their urine samples. One client is on daily supervised consumption. Have other labs had similar experiences when changing from urine methadone to EDDP assay? Is there any explanation other than adulteration?
>
> Thanks for any help offered.
>
> Steve
>
> Steve Davis,
> Principal Biochemist
> Royal Glamorgan Hospital
> Cwm Taf University Health Board
>
------------------------------
Date: Fri, 26 Jun 2015 20:19:41 +0000
From: "Heger, Nicholas" <[log in to unmask]>
Subject: Re: EDDP-negative, methadone positive urines
Hi Steve,
Per the package insert, the Roche Methadone II assay for the c501 has virtually no cross reactivity (<0.05%) with EDDP. Conversely, the Methadone Metabolite assay has almost no cross reactivity with Methadone. Therefore, I think your suspicion of adulteration is correct. Patients on therapy for opiate dependence (methadone, buprenorphine, etc.) sometimes attempt to cheat a drug test to demonstrate compliance by dissolving a small amount of the pill into the urine. If enough drug is added, this should generate a positive result on the Methadone assay, but negative by the EDDP test. Even users with reduced 2B6 and 3A4 (grapefruit juice!) activity should still generate some EDDP. Confirmation by mass spec showing a complete absence of EDDP in the sample seals the deal.
Thanks,
Nick
Nicholas Heger, PhD
Boston Children's Hospital
Tufts Medical Center & Floating Hospital for Children Clinical Chemistry Fellow Boston, MA
-----Original Message-----
From: Clinical biochemistry discussion list [mailto:[log in to unmask]] On Behalf Of Chesinta
Sent: Friday, June 26, 2015 3:41 PM
To: [log in to unmask]
Subject: Re: EDDP-negative, methadone positive urines
Hi Steve,
Multiple cytochromes metabolize methadone, before concluding on adulteration, have you considered any recent drug changes in the concerned patients ?
For example, drugs that induce CYP2B6 also induce methadone metabolism, and CYP 2B6 , of all the cytochromes has been shown to have the highest Vmax and lowest Km.
Is there more information you can provide ?
Thank you
Chesie Voma, PhD
University of Louisville
Clinical Chemistry Fellow
Sent from my Verizon Wireless 4G LTE Tablet
On Jun 22, 2015 10:40 AM, Steve Davis <[log in to unmask]> wrote:
>
> We have recently changed from a urine methadone to urine EDDP assay (both on a Roche c501) and have received enquiries from the clinical users of our service who are seeing patients negative for EDDP but who were reliably positive for methadone in the past. Our local referral lab has confirmed absence of EDDP & presence of methadone in these samples (by GC-MS), commenting that sample adulteration seems likely.
>
> There is some discussion on whether clients may be spiking their urine samples. One client is on daily supervised consumption. Have other labs had similar experiences when changing from urine methadone to EDDP assay? Is there any explanation other than adulteration?
>
> Thanks for any help offered.
>
> Steve
>
> Steve Davis,
> Principal Biochemist
> Royal Glamorgan Hospital
> Cwm Taf University Health Board
>
------------------------------
End of ACB-CLIN-CHEM-GEN Digest - 25 Jun 2015 to 26 Jun 2015 (#2015-133)
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