Hair analysis for long-term monitoring of buprenorphine intake in opioid withdrawal

Aims: Buprenorphine is a psychoactive pharmaceutical drug largely used to treat opioid withdrawal. Short-term therapeutic monitoring is commonly supported by toxicological analysis of blood and urine samples, whereas long-term monitoring by means of hair analysis is rarely used. Aim of this work was to develop and validate a highly sensitive UHPLC-MS/MS method to detect buprenorphine and norbuprenorphine in head hair. Inter-individual correlation between oral dosage of buprenorphine and head hair concentration was investigated. Furthermore, an intra-individual study by means of segmental analysis was performed on subjects with variable maintenance dosage. Methods: Hair samples from a population of 79 patients in treatment for opioid withdrawal were analyzed. The validated UHPLC-MS/MS protocol allowed to obtain LOD and LOQ values of 0.6 and 2.2 pg/mg for buprenorphine, and 6.6 and 22 pg/mg for norbuprenorphine, respectively. Validation criteria were completely satisfied, assuring selective analyte identification, with high detection capability, and precise and accurate quantification. Results and Discussion: Significant positive correlation between constant oral buprenorphine dosage (2-21 mg/die) and the sum of buprenorphine and norbuprenorphine head hair concentrations was found. Nevertheless, severe inter-individual variability limits the chance to predict the oral dosage taken by each subject from the measured concentrations of buprenorphine and norbuprenorphine in his head hair. Further source of bias and unpredictability possibly arises from the inaccuracy of self-reported real dosage intake. In contrast, strong correlation is observed in the results of the intra-individual segmental analysis, which proved reliable to detect and predict oral dosage variations during therapy for a specific subject. Remarkably, all hair samples yielded buprenorphine concentrations higher than 10 pg/mg, even when the lowest dosage was administered. Thus, this concentration can possibly be utilized as cut-off value. Conclusion: The summed up concentrations of buprenorphine and norbuprenorphine determined in head hair proved to closely reflect, on a relative scale, the dosage that each individual patient regularly takes, even if the setup of an absolute scale of linear correlation between the two parameters still appears remote, due to the significant inter-individual variability observed for the response of this biomarker. The proposed 10 pg/mg cut-off value to discriminate between regular dosage administration and occasional intake is confirmed by the present study.