Simultaneous Determination of Candesartan and Hydrochlorothiazide in Human Plasma by HPLC-MS/MS

Q3 Pharmacology, Toxicology and Pharmaceutics

Drug Development and Registration Pub Date : 2021-11-25 DOI:10.33380/2305-2066-2021-10-4-177-189

P. K. Karnakova, T. N. Komarov, O. A. Archakova, D. S. Shchelgacheva, A. V. Aleshina, N. S. Bagaeva, P. A. Karpova, I. Shohin

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引用次数: 3

Abstract

Introduction. Combined drugs have the greatest efficacy and safety in arterial hypertension treatment. The combination of candesartan and hydrochlorothiazide (AT1-receptor antagonist and a thiazide diuretic, respectively) provides high efficiency of antihypertensive combination therapy, therefore it is widely used in medical practice. Developing a method for simultaneous determination of candesartan and hydrochlorithiazide in human blood plasma is necessary for performing the analytical part of pharmacokinetic studies and bioequivalence studies of multicomponent drugs.Aim. The aim of this study is to develop a method for quantitative determination of candesartan and hydrochlorothiazide in human plasma by high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) for further bioequivalence studies.Materials and methods. Determination of candesartan and hydrochlorothiazide in human plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation. Internal standard: mixed solution of valsartan and indapamide. Mobile phase: 0.1 % formic acid solution in water (eluent A), 0.1 % formic acid in acetonitrile (eluent B). Column: Phenomenex Luna Phenyl-Hexyl, 50x4.6 mm, 5 μm. Analytical range: 2.00– 300.00 ng/mL for candesartan, 2.00–200.00 ng/mL for hydrochlorothiazide in human plasma. Ionization source: electrospray ionization. Detection conditions: 441.10 → 192.00 m/z, 441.10 → 263.15 m/z (candesartan), 295.85 → 269.00 m/z (hydrochlorothiazide), 436.00 → 207.05 m/z (valsartan), 363.85 → 132.10, 363.85 → 189.00 m/z (indapamide).Results and discussion. This method was validated by selectivity, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability. The developed method meets the requirements for conducting bioequivalence studies of medicinal products within the framework of the Eurasian Economic Union.Conclusion. The analytical range was 2.00–300.00 ng/mL for candesartan, 2.00–200.00 ng/mL for hydrochlorothiazide in human plasma. The method was applied in BE study of the combination of candesartan and hydrochlorothiazide.

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HPLC-MS/MS法同时测定人血浆中坎地沙坦和氢氯噻嗪

介绍联合用药在动脉高压治疗中具有最大的疗效和安全性。坎地沙坦和氢氯噻嗪（分别为AT1受体拮抗剂和噻嗪利尿剂）的联合治疗提供了高效的降压联合治疗，因此在医学实践中得到了广泛应用。开发一种同时测定人血浆中坎地沙坦和氢氯噻嗪的方法，对于进行多组分药物的药代动力学研究和生物等效性研究的分析部分是必要的。目标本研究的目的是建立一种用高效液相色谱-串联质谱法（HPLC-MS/MS）定量测定人血浆中坎地沙坦和氢氯噻嗪的方法，用于进一步的生物等效性研究。材料和方法。HPLC-MS/MS法测定人血浆中坎地沙坦和氢氯噻嗪的含量。样品通过乙腈蛋白质沉淀进行处理。内标：缬沙坦与吲达帕胺混合溶液。流动相：0.1%甲酸水溶液（洗脱液A），0.1%甲酸乙腈溶液（洗脱剂B）。色谱柱：Phenomenex Luna苯基己基，50x4.6 mm，5μm。分析范围：人血浆中坎地沙坦2.00–300.00 ng/mL，氢氯噻嗪2.00–200.00 ng/mL。电离源：电喷雾电离。检测条件：441.10→ 192.00 m/z，441.10→ 263.15 m/z（坎地沙坦），295.85→ 269.00 m/z（氢氯噻嗪），436.00→ 207.05 m/z（缬沙坦），363.85→ 132.10.363.85→ 189.00m/z（吲达帕胺）。结果和讨论。通过选择性、基质效应、校准曲线、准确度、精密度、加标回收率、定量下限、结转效应和稳定性对该方法进行了验证。所开发的方法符合在欧亚经济联盟框架内进行药品生物等效性研究的要求。结论：人血浆中坎地沙坦的分析范围为2.00–300.00 ng/mL，氢氯噻嗪的分析范围是2.00–200.00 ng/mL。将该方法应用于坎地沙坦和氢氯噻嗪联合用药的BE研究。

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