Bioanalytics – Chemical
2019 PharmSci 360
Traditionally, for LC-MS/MS bioanalytical assays, external calibration curves are required to achieve accurate quantitation of target analytes. Recently, a novel in-sample calibration curves (ISCC) methodology that can achieve quick and accurate LC-MS/MS bioanalysis without the use of external calibration curves was reported. The ISCC methodology utilizes the presence of multiple naturally occurring isotopologues of a stable isotopically labeled analyte to construct an in-sample calibration curve for the quantification. This methodology has great potential in many applications, for example biomarker measurement, quantitative proteomics and clinical diagnosis. Here, we assessed the feasibility of applying this ISCC−LC-MS/MS methodology in regulated bioanalysis using BMS-984478, a drug candidate, as the model compound. A LC-MS/MS method using the ISCC strategy was successfully developed and validated for the quantitative analysis of BMS-984478 in human plasma over the range of 1.33-993.42 ng/mL. We also proposed method validation procedures/processes for this new approach for industry peers’ consideration and feedback.