A Validated Stability Indicating LC-MS/MS Bio-analytical Method for Analysis of Non-Small Cell Lung Cancer Drug (Mobocertinib) in Human Plasma

Abstract

An anticancer drug mobocertinib was prescribed for the patients suffering with non-small cell lung cancer. The literature reveals that no analytical method reported for evaluation of mobocertinib in biological samples and hence this study planned to propose a simple and sensitive LCMS/MS method for quantification of mobocertinib in spiked plasma using similar action drug ribociclib as internal standard. The extraction of mobocertinib along with ribociclib was performed using a simple protein precipitation and liquid–liquid extraction with dichloromethane. The Synergi, RP 80A (100 × 4.6 mm; 4 μ) column with 0.05 M ammonium acetate at pH 4.1 with 1 % formic acid, methanol and acetonitrile at 45:25:30 (v/v) at 0.5 mL/min isocratic flow was optimized and finalized for resolution of mobocertinib and internal standard. The resolved analytes were monitored with mass analyzer operated in multiple reaction monitoring positive ion mode. The characteristic mass transition at m/z 586 → 202 and m/z 435 → 199 was observed for mobocertinib and ribociclib, respectively. The method produces calibration curve linear in the level of 0.25 ng/mL to 300 ng/mL with a sensitive detection limit of 0.075 ng/mL. The % RSD in intraday precision was calculated to be 0.64, 0.36, 0.55 and 0.68 whereas in inter-day precision was obtained as 0.95, 1.07, 0.56 and 0.28 in HQC, MQC, LQC and LLOQ, respectively. The stability during handling, extraction and as well as analyzing the mobocertinib solution was evaluated by performing various stability studies. The analytes were confirmed to be acceptable in every studied stability studies. The validation study produces acceptable results in all parameters and can successfully utilized for evaluation of mobocertinib in the biological samples.