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Abstract
This research aimed to develop a simple validated a sensitive, selective, high accurate and efficient assay for the simultaneously evaluation of Rosuvastatin and Dabigatran in human plasma using liquid chromatography tandem mass spectrometry (LC-MS/MS). Rosuvastatin-Dabigatran combines a competitive inhibitor of HMG-CoA reductase oral anticoagulant drug that acts as a direct thrombin (factor II-a) inhibitor. The design of this study was to develop special method for Rosuvastatin and Dabigatran in human plasma by a sensitive and robust (LC-MS/MS) that would result into a concurrent appraisal of Rosuvastatin and Dabigatran avoiding conversions from sample collections to assay on the LC-MS/MS-technique. The collection of sample and it procedure were optimized for Rosuvastatin influence good for Dabigatran, thus occur into an assessment simultaneously, of Rosuvastatin and Dabigatran. Liquid chromatography, Liquid-liquid extraction and coupled to confident ion mode was used according to US- FDA guidelines to evaluate and develop - validated this method. The validation parameters for calibration curves for two analytes were linear (R2 > 0.9951, n = 4) over the concentration range of 0.20 - 30.0 ng/mL for Rosuvastatin and 1 - 250 ng/mL for Dabigatran. Average extraction recoveries (improvement) 80.34 ± 9.43 for Rosuvastatin and 88.19 ± 7.13 for Dabigatran. Intra- day and inter-day run mean percent accuracy was 'tween 85.0% - 115.0% and % imprecision was <15.0%. Stability studies declare that Rosuvastatin and Dabigatran were stable in plasma during bench top (11 h at room temperature), in Injector (48 h), at the end of three successive freeze and thaw cycles and long term at -65.0°C ± 15.0°C for three months. The method was successfully tested to the pharmacokinetics parameters of Rosuvastatin and Dabigatran in healthy subjects. The simultaneously estimated method of Rosuvastatin and Dabigatran is low-cost effective, reduce analysis time and analysis cycle, enables effective utilization of resources and reduces in human volunteers bleeding burden.
Keywords: Rosuvastatin; Dabigatran; Pharmacokinetic; LC-MS/MS; Validation; Human; Plasma
1. Introduction
Rosuvastatin (RSVN), known as selective and competitive inhibitor of - (3-hydroxy-3-methyl-glutaryl-co-enzyme, A reductase known as HMG-CoA reductase. Chemically, it is bis-[(E)-7-[4-(4-fluoro-phenyl)-6-isopropyl-2- [methyl-(methyl-sulfonyl-) amino] pyrimidin-5-yl] (3R,5S)-3,5dihydroxyhept-6-enoic acid] (figure 1) [1].It fit to a group of drugs labelled statins, which lower hypercholesterolemia and related conditions and avoid cardiovascular diseases. Rosuvastatin is effective in lowering low-density lipoprotein (LDL) and cholesterol [1]. It...