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An LC-MS/MS method for determination of triple drugs combination of valsartan, amlodipine and hydrochlorothiazide in human plasma for bioequivalence study

Author(s):

Rana Said*, Basel Arafat, Tawfiq Arafat and Eyad Mallah  

Abstract:


Background: Current guidelines for the treatment of hypertension recommends the combination therapy which should control of blood pressure and enhance cardiovascular protection. Materials and Methods: A sensitive, reliable and selective tandem mass spectrometry (LC-MS/MS) method has been developed for simultaneous quantification of amlodipine (AML), valsartan (VAL) and hydrochlorothiazide (HCTZ) in human plasma. The chromatographic system was equipped with ACE 5 C8 (50 X 2.1 mm) column and utilized a mobile phase composition of 0.5 mM Ammonium Chloride & 0.04% FA-Methanol (45:55% v/v). The method used three internal standards; AML-D4,HCTZ-D2 C13 and VAL-D3 with 10% intra- and inter-day precision, 6% bias for all the analytes.

Results: The assay found to be linear with R¬2 > 0.998, the limits of quantification for AML, VAL and HCTZ were 0.2, 50.0 and 2.0 ng/mL respectively. The analytes were found to be stable in plasma samples over short and long term storage.

The developed method is rapid with a run time of 3.5 min and cost effective since simple sample preparation method is adopted. The developed method was successfully applied for bioequivalence study determination of AML, VAL, and HCTZ in human plasma after administration of fixed-dose combination tablet of (10/160/25 mg). Pharmacokinetic parameters (Cmax and AUC0-72) for AML and (Cmax, AUC0-t, AUC0-∞) for VAL and HCTZ was used for bioequivalence assessment. These were determined by using non-compartmental analysis from concentration data. Conclusion: The result showed 90% confidence intervals (obtained by ANOVA) were within the predefined ranges. As consequence, this method can be successfully applied for measuring and quantifying large number of samples.

Keywords:

Amlodipine, Valsartan, Hydrochlorothiazide, LC-MS/MS, Bioequivalence, LLE

Affiliation:

Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Jordan Center for Pharmaceutical Research (JCPR), Amman, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman



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