Desenvolvimento e validação de um método HPLC-MS/MS para a determinação de olmesartana em plasma humano

Abstract

Olmesartan medoxomil is a prodrug that, after absorption, is converted into its active form, olmesartan, belonging to the group of angiotensin II receptor blockers. The extraction and quantification techniques used for olmesartan involve complex sample preparations, generally employing Ultra High Performance Liquid Chromatography coupled to Mass Spectrometry. Thus, the development of robust and rapid alternatives is justified, such as plasma protein precipitation using simpler instrumental techniques, such as High Performance Liquid Chromatography coupled to Mass Spectrometry, for application in drug quantification. Objectives: To develop and validate a sensitive, specific and easy-to-apply analytical technique, based on protein precipitation for sample preparation, intended for the determination of olmesartan in human plasma. Methods: An HPLC-MS system (Agilent – Sciex) was used with a Luna C18 100 × 4.6 mm column and a mobile phase consisting of acetonitrile and 2 mM ammonium acetate solution with 0.125% formic acid in a 70:30 (v/v) ratio, at a flow rate of 900 µL/min. Results and Discussion: The run time was 2.3 minutes, with a linear correlation coefficient of 0.996347. The intra-run precision and accuracy evaluated at the lower limit of quantification were 12.38% and 5.00%, respectively. All validation parameters met the criteria established by RDC No. 27/2012, regarding linearity, precision, accuracy, selectivity, matrix effect and stability. Conclusion: The technique developed for the quantification of olmesartan in human plasma by LC-MS/MS proved to be simple, fast, sensitive, reproducible and suitable for application in pharmaceutical bioequivalence studies.