Buprenorphine and norbuprenorphine findings in hair during constant maintenance dosage

Abstract

It is still a matter of debate whether a positive correlation between the dose and the amount of drug in the hair exists. Drugs such as buprenorphine (BUP) used under controlled conditions present an opportunity to prove a possible relationship. Due to discrepant findings of BUP/norbuprenorphine (NBUP) ratios in hair, in vitro degradation of both analytes in diluted acid was also investigated. The levels of BUP and NBUP in proximal hair sections from 18 subjects participating in a maintenance program were determined by liquid chromatography/tandem mass spectrometry following incubation with methanol and subsequent liquid/liquid extraction. BUP and NBUP were incubated in diluted hydrochloric acid at 60°C for up to 24 h. The alleged rearrangement products were simultaneously monitored. All hair samples tested positive for BUP (lower limit of detection-0.238 ng/mg hair) and NBUP (0.043-0.961 ng/mg hair). The concentration of NBUP in hair was consistently higher than that of BUP except for a single specimen. Degradation of BUP and NBUP was dependent on time; hydrolysis of NBUP occurred faster than that of BUP. The concentration of BUP and NBUP will be underestimated if analytes are recovered by acidic procedures. NBUP should be monitored in hair samples besides BUP for the sum of both BUP and NBUP may provide an estimate of BUP exposure following long-term administration of the drug.

Buprenorphine and nor‐buprenorphine levels in head hair samples from former heroin users under Suboxone® treatment

“…Our results are in agreement with previous studies according to which the concentration of NBUP in hair was higher than that of BUP. In all the aforementioned studies, methanolic extraction or alkaline digestion of hair was performed for the isolation of BUP and NBUP. Wilkins et al .…”

“…Our results are in agreement with previous studies [8,21,22] according to which the concentration of NBUP in hair was higher than that of BUP. In all the aforementioned studies, methanolic extraction [21] or alkaline digestion [8,22] of hair was performed for the isolation of BUP and NBUP. Wilkins et al [22] evaluated the levels of BUP and NBUP in human hair, following the administration of multiples doses and found that the highest concentrations of BUP and NBUP were present in hair segments that corresponded to the period of drug treatment.…”

“…Last but not least, in another study that further reinforced the fact that NBUP is incorporated into the hair at higher levels than BUP, the authors concluded that the degradation of BUP and NBUP in acidic conditions is time‐ dependent and that the hydrolysis of NBUP occurs faster than that of BUP. Therefore, possible reasons for the discrepancies found in the reported results could be the different rate of hydrolysis between the parent drug and the metabolite, or even the procedure of extraction, since under acidic conditions the concentrations of both analytes are underestimated.…”

“…Therefore, possible reasons for the discrepancies found in the reported results could be the different rate of hydrolysis between the parent drug and the metabolite, or even the procedure of extraction, since under acidic conditions the concentrations of both analytes are underestimated. For this reason, it is now accepted that the sum of both analytes is probably the most appropriate to provide evidence of long‐term exposure …”

Issues Affecting Interpretation: Stability and Artefacts

“…Degradation of norbuprenorphine is faster than that of buprenorphine, which may serve as a likely explanation for discrepant results of hair analysis reported in the literature. The concentration of both analytes will be underestimated if recovered by acidic procedures (Cone et al 1984;Skopp et al 2011). Lactone-hydroxyl carboxylic acid interconversion presents a challenge in quantitative analysis, which typically occurs for statins (e.g.…”