Signal enhancement in HPLC-ESI-MS/MS analysis of spironolactone metabolites using HFIP and NH4F as eluent additives

Spironolactone is a synthetic steroidal antimineralocorticoid agent with a structure resembling that of the natural adrenocorticoid hormone, aldosterone. Spironolactone competes with aldosterone on aldosterone sensitive Na/K channels in the distal tubule of the nephron, thereby increasing the secretion of water and sodium while decreasing the excretion of potassium. It is rapidly and extensively metabolized in liver to at least 17 metabolites, with canrenone, 7-alpha-methylthiospironolactone, and 6-beta-hydroxy-7-alphamethylthiospironolactone as the main ones. Spironolactone has been widely used for decades and its side effects have been studied and documented. But despite being used on children for decades the dosing recommendations are based on clinical trials performed in adult population and/or expert opinion and clinical experience. As such, studies evaluating the pharmacokinetic (PK) profile of spironolactone in pediatric age-groups contribute to the refinement of evidence-based dosing recommendations in children.