A sensitive LC-MS/MS method for the determination of free maytansinoid DM4 concentrations-Method development, validation, and application to the nonclinical studies of antitumor agent DM4 conjugated hu-anti-Cripto MAb B3F6 (B3F6-DM4) in rats and monkeys

► A sensitive, specific, and high throughput method was developed and validated for the quantitation of free maytansinoid DM4 in cynomolgus monkey and Sprague Dawley rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). ► The quantitation range of the method was 0.500 - 100 ng/mL with a lower limit of quantitation of 0.500 ng/mL. ► The method was validated in monkey and rat plasma per FDA guidelinesThe validated method was employed to monitor the free DM4 levels in plasma in the IND-enabling toxicology studies of antitumor agent DM4 conjugated hu-anti-Cripto MAb B3F6 (B3F6-DM4).