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采用 UPLC-MS/MS 法测定人血浆中吲达帕胺、培哚普利及其活性代谢物培哚普利拉。

Simultaneous determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma using UPLC-MS/MS method.

机构信息

Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Beijing 100032, China.

Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Beijing 100032, China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Apr 15;1169:122585. doi: 10.1016/j.jchromb.2021.122585. Epub 2021 Mar 4.

DOI:10.1016/j.jchromb.2021.122585
PMID:33706186
Abstract

Lots of studies showed the combination therapy of perindopril, indapamide and amlodipine could increase BP lowering efficacy and the benefits of high-risk patients. To evaluate potential pharmacokinetic interaction, a simultaneous UPLC-MS/MS quantification method of perindopril, perindoprilat and indapamide in human plasma was developed and validated. The plasma samples were prepared by solid phase extraction, and then separated on an X-terra MS C (2.1 mm × 150 mm, 3.5 μm) with isocratic elution. The ion transitions at m/z 369.165 → 172.000 (perindopril), m/z 341.146 → 170.112 (perindoprilat), m/z 366.010 → 132.100 (indapamide), m/z 389.120 → 206.200 (S10211-1, IS1) and m/z 394.080 → 160.200 (S1641, IS2) were monitored under the positive ion mode of electrospray ionization with multiple reaction monitoring. This method exhibited great sensitivity, linearity, accuracy, and precision for the determination of perindopril, perindoprilat and indapamide over the range of 0.250-50.0 ng/mL. The average extraction recovery of perindopril, perindoprilat and indapamide samples at low, medium, and high concentration levels were between 85.9% and 93.6%, respectively. The stability of analytes over different storage and processing conditions in the whole study was also validated. The method is fast, accurate, sensitive and reproducible, which is suitable for the detection of the concentration of perindopril, perindoprilat and indapamide in human plasma.

摘要

许多研究表明,培哚普利、吲达帕胺和氨氯地平联合治疗可提高降压疗效和高危患者的获益。为了评估潜在的药代动力学相互作用,开发并验证了一种同时测定人血浆中培哚普利、培哚普利拉和吲达帕胺的 UPLC-MS/MS 定量方法。血浆样品经固相萃取处理,然后在 X-terra MS C(2.1mm×150mm,3.5μm)上进行等度洗脱分离。采用电喷雾正离子模式,以多反应监测方式监测 m/z 369.165→172.000(培哚普利)、m/z 341.146→170.112(培哚普利拉)、m/z 366.010→132.100(吲达帕胺)、m/z 389.120→206.200(S10211-1,IS1)和 m/z 394.080→160.200(S1641,IS2)进行离子跃迁。该方法在 0.250-50.0ng/mL 范围内对培哚普利、培哚普利拉和吲达帕胺的测定具有很高的灵敏度、线性、准确性和精密度。培哚普利、培哚普利拉和吲达帕胺低、中、高浓度水平的平均提取回收率分别在 85.9%-93.6%之间。在整个研究过程中,还验证了不同储存和处理条件下分析物的稳定性。该方法快速、准确、灵敏、重现性好,适用于人血浆中培哚普利、培哚普利拉和吲达帕胺浓度的检测。

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