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SHU Chao; XU Huaiyou; SHAO Feng; ZHAO Lijie; TAO Chunlei

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更新时间：2023-03-01

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- China Pharmacy Vol. 27, Issue 11, (2016)
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SHU Chao, XU Huaiyou, SHAO Feng, et al. [J]. China Pharmacy 27(11).(2016)
DOI：

SHU Chao, XU Huaiyou, SHAO Feng, et al. [J]. China Pharmacy 27(11).(2016) DOI：

摘要

目的：建立测定人血浆中氯吡格雷浓度的方法，研究两种硫酸氢氯吡格雷片剂的生物等效性。方法：60名健康男性受试者随机分为A、B、C、D四组，采用两制剂四周期重复交叉设计，分别空腹（A、B组）和餐后（C、D组）口服受试制剂及参比制剂各75 mg，采用液相色谱-串联质谱（LC-MS/MS）法测定人血浆中氯吡格雷的浓度。以地西泮为内标，色谱柱为Ultimate XB-C18，流动相为乙腈-0.05％甲酸溶液（84 ∶ 16，V/V），以多反应监测方式进行正离子扫描，用于定量分析的离子对分别为m/z 322.00→212.00（氯吡格雷）、m/z 285.00→154.00（内标），采用DAS 3.2.8软件计算药动学参数，以双向单侧t检验、非参数检验法考察两制剂的生物等效性。结果：氯吡格雷血药浓度在20～5 000 pg/ml范围内线性关系良好。空腹口服受试制剂或参比制剂的tmax分别为（0.850±0.356）、（0.764±0.336）h，cmax分别为（1 514.550±1 120.469）、（1 506.900±1 054.008）pg/ml，t1/2分别为（4.036±3.615）、（4.056±4.193）h，AUC0-t分别为（2 721.814±2 062.832）、（2 826.051±2 526.683）pg·h/ml；餐后口服受试制剂或参比制剂的tmax分别为（1.513±0.709）、（1.558±0.743）h，cmax分别为（5 219.509±2 711.907）、（5 520.337±3 336.664）pg/ml，t1/2分别为（5.800±4.729）、（5.513±4.206）h；AUC0-t分别为（10 890.81±4 101.357）、（11 350.653±4 174.848）pg·h/ml。两种给药条件下，受试制剂AUC0-t、AUC0-∞、cmax的90％置信区间均在参比制剂相应参数的80％～125％之内，两制剂tmax间的差异均无统计学意义（P＞0.05）。结论：该方法快速、灵敏，无杂质干扰。两种片剂生物等效。

Abstract

OBJECTIVE： To establish a method for the determination of clopidogrel in human plasma， and to study the bioequvivalence of 2 kinds of Clopidogrel hydrogen sulfate tablets. METHODS： 60 healthy male volunteers were randomly divided into group A， B， C and D. By four cycles repeated cross-over design， they were given fasting （group A and B） and postprandial （group C and D） test or reference preparation 75 mg. The concentration of clopidogrel in human plasma was determined by LC-MS/MS. Using diazepam as internal standard， Ultimate XB-C18 column was adopted with mobile phase consisted of acetonitrile-0.05％ formic acid （84 ∶ 16，V/V）. Positive ion detection was conducted in MRM mode， and monitoring transition ion-pair was m/z 322.00→212.00 for clopidogrel and m/z 285.00→154.00 for internal standard. Pharmacokinetic parameters were calculated by using DAS 3.2.8 software， and two-way and unilateral t test and non-parameters test were used to investigate the bioequivalence of two preparations. RESULTS： The linear rang of clopidogrel was 20-5 000 pg/ml. The pharmacokinetic parameters of test preparation or reference preparation after fasting oral administration were as follows： tmax were（0.850±0.356） and （0.764±0.336）h； cmax were （1 514.550± 1 120.469） and （1 506.900±1 054.008）pg/ml； t1/2 were （4.036±3.615） and （4.056±4.193）h； AUC0-t were （2 721.814±2 062.832） and （2 826.051±2 526.683） pg·h/ml. Those of test preparation or reference preparation after postprandial oral administration were as follows： tmax were （1.513±0.709） and （1.558±0.743）h； cmax were （5 219.509±2 711.907） and （5 520.337±3 336.664） pg/ml； t1/2 were （5.800±4.729） and （5.513±4.206）h； AUC0-t were （10 890.81±4 101.357）and（11 350.653±4 174.848） pg·h/ml. Under two kinds of condition， 90％CI of AUC0-t， AUC0-∞ and cmax of test preparations were 80％-125％ of corresponding parameters of reference preparations， there was no statistical significance in tmax between two preparations（P＞0.05）. CONCLUSIONS： The method is rapid， sensitive with no endogenous interference. Two tablets are bioequivalent.

关键词

硫酸氢氯吡格雷片氯吡格雷药动学生物等效性液相色谱-串联质谱法

Keywords

Clopidogrel hydrogen sulphate tabletClopidogrelPharmacokineticsBioequivalenceLC-MS/MS

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