A Simple and Sensitive LC–MS/MS Method for Simultaneous Quantification of Dasatinib and Erythromycin in Mice Plasma: Application to Preclinical Pharmacokinetic Study

ABSTRACT Dasatinib (DAS) is a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML) and erythromycin (ERY) is macrolide antibiotic used to treat a range of inflammatory conditions are often co‐administered in clinical practice. The simultaneous estimation of DAS and ERY helps in understanding the pharmacokinetics and drug–drug interactions. In this respect, we presented novel, sensitive, and validated bio‐analytical LC‐ESI‐MS/MS method for simultaneous estimation of DAS and ERY in CD‐1 mice plasma. The LLOQ was 2.0 ng/mL with an S/N ratio of 15. This validated method was used to study the PK of DAS and ERY in mice following intravenous and oral administration. The DAS was administered at 5 mg/kg via both oral and intraveneous route, whereas ERY was administered at 50 mg/kg orally and 5 mg/kg intraveneousaly. Following intravenous dosing, DAS showed high clearance and distribution, while ERY exhibited high clearance and distribution. The oral bioavailability was 64% for DAS and 21% for ERY. When co‐administered orally at 5 mg/kg for DAS and 50 mg/kg of ERY, the AUC and C max of DAS were unchanged. However, the systemic exposure (w.r.t AUC and C max ) of ERY was slightly higher (2.4‐fold) in the presence of DAS, which may be attributed because of the CYP3A4 inhibition potential.