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XU Huaiyou; SHU Chao; SHAO Feng; TAO Chunlei

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更新时间：2023-03-01

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- China Pharmacy Vol. 27, Issue 8, (2016)
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XU Huaiyou, SHU Chao, SHAO Feng, et al. [J]. China Pharmacy 27(8).(2016)
DOI：

XU Huaiyou, SHU Chao, SHAO Feng, et al. [J]. China Pharmacy 27(8).(2016) DOI：

摘要

目的：建立测定人血浆中达沙替尼浓度的方法，并研究两种片剂的生物等效性。方法：24名男性健康受试者随机分成两组，采用两制剂两周期双交叉试验设计，先后空腹及餐后口服受试制剂或参比制剂100 mg，采用液相色谱-串联质谱（LC-MS/MS）法测定人血浆中达沙替尼的浓度。以甲磺酸伊马替尼为内标，色谱柱为Welchrom C18，流动相为乙腈-0.1％甲酸水溶液（70 ∶ 30，V/V）。以多反应监测方式进行正离子扫描，采用电喷雾离子源，用于定量分析的离子对分别为m/z 488.5→401.2（达沙替尼）、m/z 494.6→394.2（内标）。用DAS 3.2.8软件进行数据处理，采用方差分析考察两种片剂的生物等效性。结果：达沙替尼血药浓度在1～300 ng/ml范围内线性关系良好。空腹口服受试制剂和参比制剂的cmax分别为（165.599±67.592）、（164.533±77.960） ng/ml，tmax分别为（1.145±0.504）、（1.080±0.467） h，t1/2分别为（5.080±2.262）、（3.771±1.596） h，AUC0-36 h分别为（550.487±256.494）、（585.986±324.885） ng·h/ml；餐后口服受试制剂和参比制剂的cmax分别为（163.058±47.533）、（165.440±53.012） ng/ml，tmax分别为（1.630±1.066）、（1.576±0.530） h，t1/2分别为（4.720±2.677）、（4.311±2.610） h，AUC0-36 h分别为（568.036±192.521）、（601.100±216.855） ng·h/ml。空腹、餐后AUC0-36 h的相对生物利用度分别为（100.2±7.5）％、（99.2±3.8）％。方差分析表明，两制剂的主要药动学参数在药物间、周期间差异均无统计学意义（P＞0.05），但在受试者个体间差异有统计学意义（P＜0.05）。结论：LC-MS/MS法能够快速测定人体血浆中达沙替尼的浓度；两种片剂生物等效。

Abstract

OBJECTIVE： To establish a method for the determination of dasatinib concentration in human plasma and study the bioequivalence of 2 kinds of tablets. METHODS： In a randomized two-way crossover study， 24 healthy male volunteers were divided into two groups， and were administered respectively with test and reference preparations 100 mg under fasting and fed conditions. The plasma concentration of dasatinib was determined by LC-MS/MS. Using imatinib mesylate as internal standard， the determination was performed on Welchrom C18 column with mobile phase consisted of acetonitrile-0.1％ formic acid （70 ∶ 30， V/V）. Positive ion scanning was conducted under MRM mode， ESI， and ion pair for quantitative analysis were m/z 488.5→401.2 （dasatinib） and m/z 494.6→394.2 （internal standard）. DAS 3.2.8 software was used for data processing and variance analysis was adopted to investigate the bioequivalence of 2 kinds of tablets. RESULTS： The linear rang of dasatinib was 1-300 ng/ml. The pharmacokinetic parameters of test and reference preparations under fasting conditions were as follows： cmax were （165.599±67.592） and （164.533±77.960） ng/ml； tmax were （1.145±0.504） and （1.080±0.467） h； t1/2 were （5.080±2.262） and （3.771±1.596） h； AUC0-36 h were （550.487±256.494） and （585.986±324.885） ng·h/ml. The pharmacokinetic parameters of test and reference preparations under fed conditions were as follows： cmax were （163.058±47.533） and （165.440±53.012） ng/ml； tmax were （1.630±1.066） and （1.576±0.530） h； t1/2 were （4.720±2.677） and （4.311±2.610） h； AUC0-36 h were （568.036±192.521） and （601.100±216.855） ng·h/ml. Relative bioavailability of AUC0-36 h under fasting and fed conditions were （100.2±7.5）％ and （99.2±3.8）％. Analysis of variance showed there were no significant difference in the pharmacokinetic parameters of between 2 preparations and cyde （P＞0.05）， there was statistical significance among subjects （P＜0.05）. CONCLUSIONS： LC-MS/MS method can determine the concentration of dasatinib in human plasma rapidly； and the two preparations are bioequivalent.

关键词

达沙替尼液相色谱-串联质谱法药动学生物等效性

Keywords

DasatinibLC-MS/MSPharmacokineticsBioequivalence

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