Method Development and Validation of Liquid Chromatography Tandem Mass Spectrometry for SLP-1A6 in Rat Plasma

SLP-1A6 is a nicardipine-derived analog that modulates the embryonic ectoderm development/Enhancer of Zeste Homolog 2 axis and holds promise as novel therapeutics for castration-resistant prostate cancer (PCa). We report here the development and validation of a robust, sensitive and specific LC-MS/MS method for quantifying SLP-1A6 in rat plasma, as part of its preclinical investigation. The method demonstrated excellent linearity, precision, accuracy, extraction recovery and stability with negligent matrix effect over a 5-2500 ng/mL concentration range. The method was successfully applied for a single intravenous dose pharmacokinetic (PK) study in adult male Sprague-Dawley rats and the resulting PK parameters were comparable to those of nicardipine, indicating that SLP-1A6 retains the favorable PK profile of the parent compound while offering in vivo efficacy for chemoresistant PCa. These findings support the further preclinical development of SLP-1A6 to overcome chemoresistance in PCa.