Biochemical assessment of spironolactone oral suspension in human plasma using ultra‐performance liquid chromatography‐tandem mass spectrometry: Application toward pharmacokinetic study

Abstract

Spironolactone is one of the non‐selective mineralocorticoid receptor antagonists acting as anti‐diuretic drugs. Spironolactone is reported to possess mild to severe hyperkalemia which could often result in fatal conditions. Although several analytical methods for evaluating spironolactone as tablet dosage forms have been established in human biological systems, it is crucial to highlight that these approaches are still limited to the suspension dosage form. In this study, we have quantified spironolactone suspension in human plasma with an efficient, sensitive, and optimized ultra‐performance liquid chromatography (UPLC)‐tandem mass spectrometry‐based bioanalytical method using a deuterated internal standard method. A reverse phase UPLC analysis and mass spectrometric detection was performed using electrospray ionization in positive ion mode as an interface, and multiple reaction monitoring as a mode of acquisition. The retention of Spironolactone (SL) and Spironolactone d7 (SL‐d7) was found to be around 6.15 and 6.07 min, respectively. The linearity range was 1.007–100.224 ng/mL for SL with 0.1 mL sample volume. The method was successfully applied to the pharmacokinetic study of spironolactone in healthy male volunteers by administrating 25 mg/5 mL oral suspension and is in accordance with bioanalytical guidelines.