Bioanalytical tandem mass spectrometry method for cinacalcet in human plasma: green assessment with advanced metrics
Anil Kollapareddy, Kousrali Sayyad, Leela Prasad Kowtharapu, Naresh Konduru, T. Mondal, Mohan Varkolu, Sreedhar Gundekari
Abstract
AIMS: This study aims to address the clinical need for managing secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients on dialysis and hypercalcemia in individuals with parathyroid carcinoma or primary hyperparathyroidism (PHPT) ineligible for parathyroidectomy. Cinacalcet, a key calcimimetic agent, targets the calcium-sensing receptor (CaSR) in the parathyroid gland to lower elevated parathyroid hormone (PTH) levels. The study focuses on developing a robust high-performance liquid chromatography tandem mass spectrometry method for cinacalcet quantification to support therapeutic monitoring and pharmacokinetics. METHODS: A bioanalytical method using cinacalcet-D3 (CCT-D3) as an internal standard and tandem mass spectrometry in positive ion mode for accurate quantification employing Triple Quad Mass spectrometer in normal mode and a Zorbax Eclipse XDB-C18 column. RESULTS: The method was comprehensively validated, demonstrating reliability through high precision, accuracy, linearity within the range of 0.300-150.00 ng/mL, and stability, all in compliance with established bioanalytical guidelines. Furthermore, its environmental sustainability was assessed using modern green chemistry evaluation metrics. CONCLUSION: This study presents a robust, selective LC-MS/MS assay for quantifying cinacalcet in human plasma. The assay demonstrates excellent linearity, precision, and recovery, making it suitable for pharmacokinetic studies, therapeutic drug monitoring, and bioequivalence or bioavailability assessments.