Tao Yi, Wang Sheng, Wang Lei, Song Min, Hang Taijun
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Jiangsu Jiayi Pharmaceutical Co., Ltd., Nanjing 210000, China.
J Pharm Anal. 2018 Oct;8(5):333-340. doi: 10.1016/j.jpha.2018.05.004. Epub 2018 May 19.
Simple and sensitive methods were developed for the determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma or whole blood by hyphenated ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Indapamide-d3, perindopril-d4 and perindoprilat-d4 were used as the internal standards. The separation was performed on a Thermo BDS Hypersil C column (4.6 mm × 100 mm, 2.4 µm) for indapamide and perindopril simultaneously following a protein precipitation pretreatment of the biosamples. The separation of perindoprilat was achieved independently on a phenomenex PFP column (4.6 mm × 150 mm, 5 µm). All the analytes were quantitated with positive electrospray ionization and multiple reactions monitoring mode. The assay exhibited a linear range of 1-250 ng/mL for indapamide, 0.4-100 ng/mL for perindopril and 0.2-20 ng/mL for perindoprilat. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, recovery, reproducibility, stabilities and matrix effects, and successfully applied to the pharmacokinetic study of perindopril tert-butylamine/indapamide compound tablets in Chinese healthy volunteers and the comparative pharmacokinetic study between plasma and whole blood.
建立了简单灵敏的超高效液相色谱-质谱联用（UPLC-MS/MS）法，用于测定人血浆或全血中的吲达帕胺、培哚普利及其活性代谢产物培哚普利拉。以吲达帕胺-d3、培哚普利-d4和培哚普利拉-d4作为内标。生物样品经蛋白沉淀预处理后，在Thermo BDS Hypersil C柱（4.6 mm×100 mm，2.4 µm）上同时分离吲达帕胺和培哚普利。培哚普利拉则在phenomenex PFP柱（4.6 mm×150 mm，5 µm）上单独分离。所有分析物均采用正电喷雾电离和多反应监测模式进行定量。该方法对吲达帕胺的线性范围为1-250 ng/mL，对培哚普利为0.4-100 ng/mL，对培哚普利拉为0.2-20 ng/mL。该方法在准确性、精密度、回收率、重现性、稳定性和基质效应等方面均经过充分验证，符合生物分析要求，并成功应用于培哚普利叔丁胺/吲达帕胺复方片剂在中国健康志愿者中的药代动力学研究以及血浆和全血之间的比较药代动力学研究。
