LC-MS/MS法测定阿片依赖者尿中丁丙诺啡及其代谢物和纳诺酮浓度  

Determination of buprenorphine and its metabolite and naloxone in urine from opioid-dependent subjects by LC-MS/MS

作　　者：刘霞[1,2] 倪晓佳[1] 尚德为[1] 张明[1] 胡晋卿[1] 王占璋[1] 邱畅[1] 温预关[1] 

机构地区：[1]广州医科大学附属脑科医院药学部,广东广州510370 [2]山东省交通医院药剂科,山东济南250031

出　　处：《广东药学院学报》2014年第2期136-141,共6页Academic Journal of Guangdong College of Pharmacy

基　　金：广东华南药物临床试验公共服务平台建设/广东省重大科技专项立项资助(2011A080300003);国家临床重点专科资助项目(20121007);广东省药学会医院药学研究基金(奥赛康基金)(2013A12)

摘　　要：目的 建立简单、快速的LC-MS/MS法,用于测定阿片依赖者尿中丁丙诺啡及其代谢物N-去烷基丁丙诺啡和纳诺酮的浓度,并进行尿排泄动力学研究.方法 尿样经NaOH碱化后进行液液萃取,丁丙诺啡以曲马多为内标、正己烷进行提取,N-去烷基丁丙诺啡和纳诺酮则以纳美芬为内标、乙酸乙酯-二氯甲烷（体积比4∶1）进行提取;质谱检测采用正离子模式,电喷雾离子化,多反应监测方式测定样品浓度;12名阿片依赖者口服复方丁丙诺啡纳诺酮舌下片4片（丁丙诺啡8 mg∶纳洛酮2 mg）,计算尿中排泄率和尿药动力学参数,以考察排泄情况.结果 丁丙诺啡、N-去烷基丁丙诺啡和纳诺酮的线性范围分别为0.05 ～ 20 μg/L、1 ～ 200 μg/L和1～ 500 μg/L,定量下限分别为0.05 μg/L、1μg/L和1μg/L,提取回收率均大于76％,日内、日间RSD均小于8.4％;尿中排泄率分别为0.90％、2.13％和30.01％.结论 该法简单、快速、专属性强、重复性好,可用于阿片依赖者尿中丁丙诺啡、N-去烷基丁丙诺啡和纳诺酮浓度测定及排泄药动学研究.Objective To develop a simple and rapid LC-MS/MS method for the determination of buprenorphine and its metabolite norbuprenorphine （NBUP） and naloxone in urine from opioid-dependent subjects and study its excretion pharmacokinetics. Methods After urine alkalified, buprenorphine and internal standard （IS） were extracted with n-hexane, while acetic ether： dichlommethane （ 4 ： 1 ） were used for norbuprenorphine, naloxone and IS, respectively. Positive ion mode was used with multiple reactions monitoring （MRM） by using electrospray ionization （ESI）. Excretion rates were studied in 12 opioid- dependent subjects after oral administration of four compound buprenorphine naloxone sublingual tablets （buprenorphine 8 mg： naloxone 2 mg）.Results The calibration curves of buprenorphine, norbuprenorphine and naloxone were linear ranging from 0.05-20 μg/L, 1- 200 μg/L, and 1- 500 μg/L.The lower limit of quantification were 0.05 μg/L, 1 μg/L and 1 μg/L. The recoveries were more than 76%.The intra and inter-day precision were less than 8.4%.Excretion rates were 0.90%,2.13% and 30.01%, respectively. Conclusion The method is simple, rapid, and accurate, which can be applied to determine buprenorphine, norbuprenorphine and naloxone concentration in urine and excretion pharmacokinetics.

关 键 词：丁丙诺啡N-去烷基丁丙诺啡 纳诺酮 LC-MS MS 排泄动力学 

分 类 号：R927.2[医药卫生—药学]