Objective: The inadvertent combination of sildenafil (SLD) and nitric oxide releasing compounds (NRC) may cause a life threatening hypotension and conversion of coital angina into an irreversible one. The aim of this study was to develop and validate a UPLC MS/MS method for the simultaneous quantitative analysis of SLD, nicorandil (NRD), and ARG in human plasma to determine the safety margins for drug combinations.
Design and method: Chromatographic elution was achieved in 4min using gradient elution and an injection volume of 10μL. Electro-spray positive ionization (ESI+ve) detection and multiple-reaction monitoring mode (MRM) were used for detection.
Results: The method was found to be linear (10-900ng/mL for SLD and NRD while 1-30μg/mL for ARG), accurate and precise (99.35±1.58, 99.62±1.13, and 100.04±1.22% for SLD, NRD and ARG; respectively) and met all other validation requirements.
Conclusion: The developed UPLC MS/MS method is suitable for fast, sensitive, accurate and simultaneous determinations of SLD, NRD, and ARG in plasma.
Keywords: Drug interactions; LC–MS/MS; Nicorandil; Sildenafil citrate; l-Arginine.
Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.