UPLC-MS/MS法测定人全血中吲达帕胺浓度及其生物等效性研究  

Determination of the content of indapamide in human whole blood by UPLC-MS/MS method and study on its bioequivalence

作　　者：郑桂茹[1] 张梦琪[2] 张荷丽[3] 陆晓佩 董春霞[2] 曹维锷[4] ZHENG Guiru;ZHANG Mengqi;ZHANG Heli;LU Xiaopei;DONG Chunxia;CAO Weie(Department of Pharmacy,Jinhua People’s Hospital,Zhejiang Jinhua 321000,China;Central Laboratory,Shanghai Xuhui Central Hospital,Shanghai Engineering Research Center of Phase Ⅰ Clinical Research and Quality Consistency Evaluation for Drugs,Shanghai 200031,China;Department of Medicine,Yaopharma Co.,Ltd.,Chongqing 401121,China;Department of Emergency,Shanghai Xuhui Central Hospital,Shanghai 200031,China)

机构地区：[1]浙江省金华市人民医院药剂科,浙江金华321000 [2]上海市徐汇区中心医院中心实验室,上海药物Ⅰ期临床暨药物一致性评价工程技术研究中心,上海200031 [3]重庆药友制药有限责任公司医学部,重庆401121 [4]上海市徐汇区中心医院急诊科,上海200031

出　　处：《药学服务与研究》2020年第3期193-197,共5页Pharmaceutical Care and Research

摘　　要：目的:建立测定人全血中吲达帕胺浓度的超高效液相色谱联用质谱(UPLC-MS/MS)法,并应用于其生物等效性研究。方法:以氘3-吲达帕胺为内标,用乙腈对全血进行蛋白沉淀。色谱柱为Acquity UPLC BEH C18柱(50 mm×2.1 mm,1.7μm);流动相为含0.001%甲酸和0.5 mmol/L甲酸铵的水溶液-乙腈(60∶40,V/V),流速为0.6 ml/min;进样量3μl。采用负离子多反应监测(MRM)扫描分析,离子通道分别为m/z 364.0→188.9(吲达帕胺),m/z 367.0→188.9(氘3-吲达帕胺)。结果:吲达帕胺的线性范围为3~300 ng/ml(r>0.999),准确率为93.11%~105.1%,批内、批间RSD均<5.76%。药动学参数cmax、AUC0~t、AUC0~∞几何均值比值的90%置信区间分别为113.00%~124.13%、99.49%~103.67%和99.00%~103.57%。重庆药友制药有限责任公司生产的吲达帕胺片(2.5 mg/片)与法国Les Laboratoires Servier公司生产的吲达帕胺片(2.5 mg/片)具有生物等效性。结论:本方法简便、快捷,特异性强,准确可靠,适用于吲达帕胺的生物等效性研究。Objective:To establish an ultra high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method for content determination of indapamide in human whole blood and apply it to the study of bioequivalence.Methods:Deuterium 3-indapamide was used as an internal standard and acetonitrile was applied for protein precipitation of whole blood.The column was Acquity UPLC BEH C18 column(50 mm×2.1 mm,1.7μm),the mobile phase was an aqueous solution containing 0.001%formic acid and 0.5 mmol/L ammonium formate-acetonitrile(60∶40,V/V),the flow rate was 0.6 ml/min,the injection volume was 3μl.Negative ion multiple reaction monitoring(MRM)scanning analysis was applied with the ion channels being m/z 364.0→188.9(indapamide),m/z 367.0→188.9(deuterium 3-indapamide).Results:The linear range of indapamide was 3-300 ng/ml(r>0.999),the accuracy was 93.11%-105.1%,and the intra-and inter-batch RSD was both<5.76%.The 90%confidence intervals for the geometric mean ratios of cmax,AUC0-t and AUC0-∞were 113.00%-124.13%,99.49%-103.67%and 99.00%-103.57%,respectively.Indapamide tablets(2.5 mg per tablet)produced by Yaopharma Co.,Ltd.and indapamide tablets(2.5 mg per tablet)produced by the French Les Laboratoires Servier were bioequivalent.Conclusion:This method is simple,rapid,specific,accurate and reliable,and is suitable for bioequivalence study of indapamide.

关 键 词：吲达帕胺 色谱法 高效液相 质谱法 联用 生物等效性 

分 类 号：R972.4[医药卫生—药品] R927.2[医药卫生—药学]