DATE: September 5, 2018
TIME: 8:00AM PDT
A New Paradigm for Buprenorphine Testing
Buprenorphine (BUP) is a partial mu-agonist synthetic opioid, an important drug for treating opioid use disorder. BUP is often prescribed as a sublingual co-formulation with the opioid antagonist naloxone (NXO) to deter illicit parenteral use and diversion. Best practice recommendations include monitoring for BUP prescription compliance by testing urine for BUP and the metabolites BUP-glucuronide, norbuprenorphine (NBP) and NBP-glucuronide or by testing for total BUP and total NBP after glucuronide hydrolysis. In this webinar we will review the pharmacokinetics of BUP, NBP and NXO and then discuss strategies for optimizing automated sample preparation with the Tecan AC Extraction PlateTM for LC-MS/MS analysis of these analytes. Our question was – could we simplify the analysis by measuring only free BUP, NBP and NXO at sufficiently low quantitation limits such that no false negatives would occur? If so – we could avoid the time consuming and expensive glucuronide hydrolysis step or alternatively the more labor-intensive measurement of both free and glucuronide analytes. After validating limits of quantitation of 0.2 ng/mL (free BUP), 0.5 ng/mL (free NBP), and 5 ng/mL (free NXO) we compared results for free and total BUP, NBP and NXO in 222 patient samples. The results of that study support monitoring for BUP compliance using positive/negative cutoffs of 0.2 and 0.5 ng/mL for free BUP and free NBP respectively. We will review the results of the method validation, the distributions of free, total, and % free BUP, NBP and NXO concentrations in this cohort and discuss interpretation for individual samples of interest.
• Diagram the metabolism of sub-lingual buprenorphine/naloxone and list the relative and range of concentrations of free and total buprenorphine, metabolites and naloxone to be expected in urine samples.
• Describe the chemistry and process for AC plate extraction.
• List the characteristics of a compound suitable for extraction with the AC plate and explain how pH modification of extraction and elution reagents may improve extraction recovery for weak acids/bases.