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

  • J Chromatogr Sci. 2026 Feb 13;64(3):bmag004. doi: 10.1093/chromsci/bmag004.
Yuan Chen  1 Tolulope Adebusuyi  1 Edwina Oppong  1 Edidiong Abraham  1 Yen Maroney Lawrence  1 Jing Ma  1 Dong Liang  1 San L Pham  2 Frank E McDonald  2 Alira Danaher  3 Daqing Wu  3 Huan Xie  1
Affiliations
  • 1. College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA.
  • 2. Department of Chemistry, Emory University, 1515 Dickey Dr., Atlanta, GA 30322 USA.
  • 3. Center for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, 223 James P Brawley Dr SW, Atlanta, GA 30314, USA.
Abstract

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.

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