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

BACKGROUND:: Buprenorphine is a psychoactive pharmaceutical drug largely used to treat opiate addiction. Short-term therapeutic monitoring is 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. METHODS:: 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. Hair samples from a population of 79 patients in treatment for opiate addiction were analyzed. RESULTS:: The validated UHPLC-MS/MS protocol allowed to obtain limits of detection and quantification at 0.6 and 2.2 pg/mg for buprenorphine, and 5.0 and 17 pg/mg for norbuprenorphine, respectively. Validation criteria were satisfied, assuring selective analyte identification, high detection capability, precise and accurate quantification. Significant positive correlation was found between constant oral buprenorphine dosage (1-32 mg/day) and the summed up head hair concentrations of buprenorphine and norbuprenorphine. Nevertheless, substantial inter-individual variability limits the chance to predict the oral dosage taken by each subject from the measured concentrations in head hair. In contrast, strong correlation is observed in the results of intra-individual segmental analysis, which proved reliable to detect oral dosage variations during therapy. CONCLUSIONS:: Remarkably, all hair samples yielded buprenorphine concentrations higher than 10 pg/mg, even when the lowest dosage was administered. Thus, these results support the selection of 10 pg/mg as a cut-off value.