Vincent F, Bessard J, Vacheron J, Mallaret M, Bessard G
Laboratoire de Pharmacologie et Analyses Toxicologiques, Centre Hospitalier Universitaire de Grenoble, France.
J Anal Toxicol. 1999 Jul-Aug;23(4):270-9. doi: 10.1093/jat/23.4.270.
Buprenorphine, which is used in France as a substitution drug for opioid addiction, is widely abused, and several fatal cases have been reported. In order to confirm a recent intoxication or to establish retrospectively chronic abuse, a simple and reliable gas chromatographic-mass spectrometric method was developed and validated for quantitation of buprenorphine and its active metabolite norbuprenorphine in urine and hair. Two milliliters of urine or 50 mg of pulverized hair was submitted to a pretreatment (enzymatic hydrolysis for urine and decontamination with dichloromethane followed by incubation in 0.1 M HCI for hair). Buprenorphine-d4 was chosen as the internal standard. Selective solid-phase extraction with Bond Elut Certify columns provided recoveries higher than 85% for urine and 43% for hair. By using a mixture of MSTFA/TMSIM/TMCS (100:2:5), buprenorphine and norbuprenorphine produced stable silylated derivatives. The detection was carried out with a quadrupole mass detector working in El selected ion monitoring mode. Ions at m/z 450 and 468 were chosen for the quantitation of buprenorphine and norbuprenorphine, respectively (m/z 454 was used for the internal standard). Limits of quantitation were 0.25 and 0.20 ng/mL, respectively, for buprenorphine and norbuprenorphine in urine and 0.005 ng/mg for the two compounds in hair. Calibration curves were linear from 0 to 50 ng/mL in urine and from 0 to 0.4 ng/mg in hair. Between-day and within-day precisions were less than 8.4% in hair and 6.1% in urine for both molecules in all cases. This method was applied to urine and hair samples collected from patients in a withdrawal treatment program and demonstrated its good applicability in routine analysis and its benefit for clinicians. This technique, which requires instruments already available to many toxicology laboratories, offers an attractive alternative to more sophisticated techniques.
丁丙诺啡在法国被用作阿片类药物成瘾的替代药物，但却被广泛滥用，已有多起致死案例报道。为了确认近期的中毒情况或回顾性地确定长期滥用情况，开发并验证了一种简单可靠的气相色谱 - 质谱法，用于定量尿液和毛发中的丁丙诺啡及其活性代谢物去甲丁丙诺啡。将两毫升尿液或50毫克粉碎后的毛发进行预处理（尿液进行酶解，毛发先用二氯甲烷去污，然后在0.1 M盐酸中孵育）。选择丁丙诺啡 - d4作为内标。使用Bond Elut Certify柱进行选择性固相萃取，尿液的回收率高于85%，毛发的回收率为43%。通过使用MSTFA/TMSIM/TMCS（100:2:5）混合物，丁丙诺啡和去甲丁丙诺啡产生稳定的硅烷化衍生物。检测采用在电子轰击选择离子监测模式下工作的四极杆质量检测器进行。分别选择m/z 450和468的离子用于定量丁丙诺啡和去甲丁丙诺啡（m/z 454用于内标）。尿液中丁丙诺啡和去甲丁丙诺啡的定量限分别为0.25和0.20 ng/mL，毛发中这两种化合物的定量限为0.005 ng/mg。尿液中校准曲线在0至50 ng/mL范围内呈线性，毛发中在0至0.4 ng/mg范围内呈线性。在所有情况下，两种分子在毛发中的日间和日内精密度均小于8.4%，在尿液中均小于6.1%。该方法应用于从戒毒治疗项目患者中收集的尿液和毛发样本，证明了其在常规分析中的良好适用性以及对临床医生的益处。这种技术只需许多毒理学实验室已有的仪器，为更复杂的技术提供了有吸引力的替代方案。
