摘要
本试验建立了液相色谱-串联质谱联用法(LC/MS/MS)测定了10名健康受试者单剂量口服试验制剂多潘立酮片剂(西安杨森制药有限公司生产)10 mg后,人血浆中不同时刻多潘立酮的浓度,绘制出了血药浓度-时间曲线。根据不同时刻的血药浓度数据,采用Topfit 2.0软件求算出主要的药代动力学参数。
试验中选用曲马多作为内标物,血浆样品经液-液萃取后,以甲醇:0.5%氨水(80:20,v/v)为流动相,采用Zorbax XDB-C8柱分离,通过API 4000型三重四极杆串联质谱仪以MRM方式进行检测。与国内外相关文献报导的检测方法相比,本试验所建立的LC/MS/MS法更为灵敏、快速且专属性强,更为重要的一点,本法仅需100μl的血浆样品即可进行定量分析,大大地减少了健康受试者所受的损伤,提高了受试者的顺应性。本方法线性范围为0.3-100 ng/ml,最低定量浓度为0.3 ng/ml,方法确证结果表明,本方法具有良好的精密度与准确度、提取回收率和稳定性,适合多潘立酮的人体药代动力学研究。
10名健康受试者单剂量口服试验制剂多潘立酮片剂10 mg后,血浆中多潘立酮的Tmax为0.60±0.30 h(平均值±标准差,下同);Cmax为11.20±4.83 ng/ml;t1/2为8.52±0.99 h;采用梯形法计算,AUC0-36分别为44.35±12.65 ng·h/ml,AUC0-∞分别为46.44±13.71 ng·h/ml。
OBJECTIVE: To develop a LC/MS/MS method for the determination of domperidone in human plasma and to study its pharmacokinetics in healthy volunteers .
METHOD: The analyte was extracted from plasma samples by liquid-liquid extraction, separated through a Zorbax XDB-C8 column and detected by tandem mass spectrometry with an electrospray ionization interface. The concentrations of domperidone in human plasma samples at different time points were determined by LC/MS/MS and the plasma concentrations-time profiles were obtained. The pharmacokinetic parameters were described by the obtained data. RESULTS: The assay was linear over the concentration range of 0.3?100 ng/ml with a limit of quantitation (LOQ) of 0.3 ng/ml. The inter- and intra-day precision and accuracy were within±15%. The main pharmacokinetic parameters were as follows: Cmax was 11.20±4.83 ng/ml occurring at 0.60±0.30 h, the mean plasma elimination half-life (t1/2) was 8.52±0.99 h and the AUC0?36 and AUC0?∞were 44.35±12.65 and 46.44±13.71 ng.h/ml, respectively.
CONCLUSION: The LC/MS/MS method was suitable for the pharmacokinetic study of domperidone in human with the advantage of specificity, sensitivity, accuracy and high speed.
引文
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