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[药代动力学研究中采用液相色谱-串联质谱法测定人血浆中的阿那拉唑]

[Determination of anaprazole in human plasma by LC-MS/MS in pharmacokinetic study].

作者信息

Cheng Dong-xia, Dai Xiao-jian, Zhang Yi-fan, Wu Yong-qian, Shi Chong-tie, Ma Xi-feng, Li Jin, Chen Xiao-yan, Zhong Da-fang

出版信息

Yao Xue Xue Bao. 2016 Dec;51(12):1885-90.

PMID:29908560
Abstract

Anaprazole is a proton pump inhibitor clinically used for curing peptic ulcer. A rapid, sensitive and convenient LC-MS/MS method was first established for the determination of anaprazole in human plasma. d(3), (13)C-anaprazole was used as internal standard (IS). After extraction from human plasma by protein precipitation with acetonitrile, all components were separated on an Extend C(18) column (100 mm × 4.6 mm, 3.5 μm). The assay was linear over the concentration range of 5.00-3 000 ng·m L(-1) (r(2) > 0.995). The method was successfully applied to a pharmacokinetic study of 40 mg anaprazole enteric-coated tablets in 14 Chinese healthy volunteers under fasting or high fat diet conditions. C(max) was (1 020 ± 435) ng·m L(-1) and AUC(0-t) was (2 370 ±754) h·ng·m L(-1) under fasting condition. And C(max) was (538 ± 395) ng·m L(-1) and AUC(0-t) was (1 610 ± 650) h·ng·m L(-1) under high fat diet condition. The plasma results suggest that the exposure of anaprazole is reduced by the high fat diet.

摘要

阿那拉唑是一种临床上用于治疗消化性溃疡的质子泵抑制剂。首次建立了一种快速、灵敏且便捷的液相色谱-串联质谱法(LC-MS/MS)用于测定人血浆中的阿那拉唑。d(3),(13)C-阿那拉唑用作内标(IS)。通过乙腈沉淀蛋白从人血浆中提取后,所有成分在Extend C(18)柱(100 mm×4.6 mm,3.5μm)上进行分离。该测定法在5.00 - 3000 ng·mL(-1)浓度范围内呈线性(r(2)>0.995)。该方法成功应用于14名中国健康志愿者在禁食或高脂饮食条件下对40 mg阿那拉唑肠溶片的药代动力学研究。禁食条件下,C(max)为(1020±435) ng·mL(-1),AUC(0 - t)为(2370±754) h·ng·mL(-1)。高脂饮食条件下,C(max)为(538±395) ng·mL(-1),AUC(0 - t)为(1610±650) h·ng·mL(-1)。血浆结果表明高脂饮食会降低阿那拉唑的暴露量。

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