(115) Interpretation of urine drug testing results in patients using transdermal buprenorphine preparations for the treatment of chronic non-cancer pain

Abstract

The use of buprenorphine for the management of chronic pain has risen rapidly since the FDA approved a transdermal formulation of this opioid in 2010. Consensus guidelines for the use of chronic opioid therapy highlight the importance of routine monitoring for patience compliance using periodic urine drug screens. The validity of the urine buprenorphine detection assay, currently in widespread use, was established for monitoring patient compliance in patients receiving sublingual formulations (e.g. subutex, suboxone) in the outpatient addiction treatment setting. However, transdermal dosing is an order of magnitude lower (mcg range) than sublingual (mg range). This retrospective analysis of tandem LC-MS urine samples from a single reference laboratory compares the results from two different buprenorphine treatment cohorts: transdermal pain treatment and sublingual detoxification. Samples from the group (n=54) undergoing pain treatment with the transdermal formulation showed urine concentrations of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine glucuronide significantly lower than the range of those treated with sublingual preparations (often below the 5mcg/ml limit of detection). The analyte that differed the most between the two patient groups was norbuprenorphine, detected in only 16.2% of transdermal patients with an overall median concentration of < 3 ng/mL, versus 100% of sublingual patients with a median concentration of 88 ng/mL. Buprenorphine-glucuronide demonstrated the highest positive rate of detection at 97.3% in samples from the transdermal group with at least one positive detectable analyte. This study demonstrates that urine parent drug and metabolite profiles are markedly different for the distinct patient populations using sublingual and transdermal buprenorphine formulations. Failure to recognize the difference in urine concentrations may lead to a misinterpretation of noncompliance. Assays with high sensitivity for buprenorphine glucuronide will likely have greater relevance in the pain treatment setting. The use of buprenorphine for the management of chronic pain has risen rapidly since the FDA approved a transdermal formulation of this opioid in 2010. Consensus guidelines for the use of chronic opioid therapy highlight the importance of routine monitoring for patience compliance using periodic urine drug screens. The validity of the urine buprenorphine detection assay, currently in widespread use, was established for monitoring patient compliance in patients receiving sublingual formulations (e.g. subutex, suboxone) in the outpatient addiction treatment setting. However, transdermal dosing is an order of magnitude lower (mcg range) than sublingual (mg range). This retrospective analysis of tandem LC-MS urine samples from a single reference laboratory compares the results from two different buprenorphine treatment cohorts: transdermal pain treatment and sublingual detoxification. Samples from the group (n=54) undergoing pain treatment with the transdermal formulation showed urine concentrations of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine glucuronide significantly lower than the range of those treated with sublingual preparations (often below the 5mcg/ml limit of detection). The analyte that differed the most between the two patient groups was norbuprenorphine, detected in only 16.2% of transdermal patients with an overall median concentration of < 3 ng/mL, versus 100% of sublingual patients with a median concentration of 88 ng/mL. Buprenorphine-glucuronide demonstrated the highest positive rate of detection at 97.3% in samples from the transdermal group with at least one positive detectable analyte. This study demonstrates that urine parent drug and metabolite profiles are markedly different for the distinct patient populations using sublingual and transdermal buprenorphine formulations. Failure to recognize the difference in urine concentrations may lead to a misinterpretation of noncompliance. Assays with high sensitivity for buprenorphine glucuronide will likely have greater relevance in the pain treatment setting.