Pirro Valentina, Fusari Ivana, Di Corcia Daniele, Gerace Enrico, De Vivo Enrico, Salomone Alberto, Vincenti Marco
*Department of Chemistry, University of Turin; †Regional Antidoping and Toxicology Center "A. Bertinaria," Orbassano; and ‡Addiction Department 1, ASL Torino 2, Turin, Italy.
Ther Drug Monit. 2014 Dec;36(6):796-807. doi: 10.1097/FTD.0000000000000078.
Buprenorphine (BUP) 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 ultrahigh-performance liquid chromatography tandem mass spectrometry method to detect BUP and norbuprenorphine (NBUP) in head hair.
Interindividual correlation between oral dosage of BUP 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.
The validated ultrahigh-performance liquid chromatography tandem mass spectrometry protocol allowed to obtain limits of detection and quantification at 0.6 and 2.2 pg/mg for BUP and 5.0 and 17 pg/mg for NBUP, respectively. Validation criteria were satisfied, assuring selective analyte identification, high detection capability, and precise and accurate quantification. Significant positive correlation was found between constant oral BUP dosage (1-32 mg/d) and the summed up head hair concentrations of BUP and NBUP. Nevertheless, substantial interindividual variability limits the chance to predict the oral dosage taken by each subject from the measured concentrations in head hair. In contrast, strong correlation was observed in the results of intra-individual segmental analysis, which proved reliable to detect oral dosage variations during therapy.
Remarkably, all hair samples yielded BUP 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 cutoff value.
丁丙诺啡(BUP)是一种主要用于治疗阿片类药物成瘾的精神活性药物。血液和尿液样本的毒理学分析可支持短期治疗监测,而通过毛发分析进行长期监测则很少使用。这项工作的目的是开发并验证一种高灵敏度的超高效液相色谱串联质谱法,用于检测头发中的丁丙诺啡(BUP)和去甲丁丙诺啡(NBUP)。
研究了BUP口服剂量与头发浓度之间的个体间相关性。此外,还对维持剂量可变的受试者进行了分段分析的个体内研究。分析了79名接受阿片类药物成瘾治疗患者的头发样本。
经过验证的超高效液相色谱串联质谱方法分别获得了BUP的检测限和定量限为0.6和2.2 pg/mg,NBUP的检测限和定量限为5.0和17 pg/mg。满足了验证标准,确保了选择性分析物鉴定、高检测能力以及精确和准确的定量。发现恒定口服BUP剂量(1 - 32 mg/d)与BUP和NBUP的头发总浓度之间存在显著正相关。然而,个体间的巨大差异限制了根据头发中测得的浓度预测每个受试者口服剂量的机会。相比之下,个体内分段分析结果显示出强烈的相关性,这证明在治疗期间检测口服剂量变化是可靠的。
值得注意的是,即使给予最低剂量,所有头发样本的BUP浓度均高于10 pg/mg。因此,这些结果支持选择10 pg/mg作为临界值。