复方丁丙诺啡纳洛酮舌下片在阿片类药物依赖者中的药动学  

Determination and pharmacokinetics of compound buprenorphine/naloxone sublingual tablet in plasma from opioid-dependent subjects

作　　者：刘霞[1,2] 倪晓佳[1] 李广兰[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：《中国医院药学杂志》2014年第21期1808-1813,共6页Chinese Journal of Hospital 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;编号:2011A080300003)

摘　　要：目的：建立液相-串联质谱（LC-MS/MS）法测定阿片类药物依赖者舌下含服复方丁丙诺啡纳洛酮后,血浆中丁丙诺啡及其代谢物去环丙甲基丁丙诺啡、纳洛酮的浓度并进行药动学考察。方法：血浆样品经氢氧化钠碱化后,丁丙诺啡以曲马多为内标,加正己烷提取;代谢物和纳洛酮则以纳美芬为内标,加醋酸乙酯-二氯甲烷（4∶1）提取。12名受试者舌下含服复方丁丙诺啡纳洛酮舌下片16 mg后于不同时间点采血,LC-MS/MS法检测浓度并用DAS软件计算药动学参数。结果：丁丙诺啡、代谢物及纳洛酮分别在50～20 000 ng·L^-1、50～10 000 ng·L^-1和20～2 000 ng·L^-1内线性关系良好,定量下限分别为50ng·L-1、50 ng·L^-1、20 ng·L^-1;提取回收率〉68.3%,日内、日间RSD小于8.9%。主要药动学参数Cmax分别为（3.9±2.0）、（1.8±1.5）和（0.6±0.3）μg·L-1;t1/2分别为（35.9±12.7）、（35.8±12.0）和（1.7±0.5）h;AUC（0-∞）分别为（41.3±17.5）、（43.0±17.7）和（1.2±0.4）μg·h·L-1。结论：该法简单、快速、灵敏、准确,可用于人体血药浓度测定及药动学考察。OBJECTIVE To establish a LC-MS/MS method for the determination of buprenorphine （BLIP） and its metabolite norbuprenorphine （NBUP） and naloxone in plasma from opioid-dependent subjects and apply to pharmacokinetic study. METttODS After plasma alkalified with sodium hydroxide, BUP and internal standard （IS） were extracted with n-hexane, while acetic ether： dichlomethane （4： 1） were used for NBUP and naloxone, respectively. 12 subjects received an administration of compound buprenorphine/naloxone sublingual tablet 16 mg by s. 1. and plasma samples were collected and pharmacokinetic parameters were calculated by DAS. RESULTS The calibration curves of BUP, NBUP and naloxone were linear over the range of 50 - 20 000 ng·L^-1 , 50 - 10 000 ng·L^-1 , and 20- 2 000 ng·L^-1, respectively. The lower limit of quantification was 50 ng.L^-1, 50 ng·L^-1, and 20 ng·L^-1 , respectively. The recoveries were more than 68. 3%. The intra and interday precision were less than 8. 9%. Major pharmacokinetic parameters were as follows： Cmax were （3. 9 ± 2. 0）, （1.8 ± 1.5） and （0. 6 ± 0. 3）μg·L-1 ; h/2 were （35.9 ± 12. 7）, （35.8 ± 12. 0） and （1.7 ± 0. 5） h; AUC（0-∞） were （41.3 ± 17. 5）, （43.0 ± 17. 7） and （1.2 ± 0. 4）μg·h· L-1. CONCLUSION The method is simple, rapid, sensitive and accurate and can be applied in plasma concentration investigation and pharmacokinetic study.

关 键 词：丁丙诺啡 去环丙甲基丁丙诺啡 纳洛酮 液相-串联质谱法 药动学 

分 类 号：R966[医药卫生—药理学]