Green Ultra-Fast UPLC-MS/MS Method for Enasidenib Quantification in HLMs Matrix With the Metabolic Stability Assessment: In Silico Study for Structural Alerts, ADME Characteristics and Metaboslic Lability #MMPMID41351223
Attwa MW; Abdelhameed AS; Ali AM; AlRabiah H; Kadi AA
Biomed Chromatogr 2026[Jan]; 40 (1): e70297 PMID41351223show ga
Enasidenib (ESD), an oral medication, was used for the treatment of patients with refractory or relapsed Acute Myeloid Leukemia. No prior UPLC-MS/MS method with combined green metrics and in silico metabolism analysis for ESD was reported, so the research sought to establish an ultrafast UPLC-MS/MS method for estimating ESD in the HLMs matrix. The MS/MS analysis was applied applying positive ESI ionization mode, and chromatography using an Eclipse Plus C8 column (reversed phase) within one minute. The UPLC-MS/MS method exhibited a good degree of greenness as approved by the MoGAPI score (68.0) and the AGREE score (0.66). The linearity range was form 1 ng/mL (LOQ) to 4000 ng/mL. The precision and accuracy for intraday and interday measurements varied from -3.11% to 10.67% and -7.22% to 12.33%, respectively. The in vitro t(1/2) and the intrinsic clearance (Cl(int)) were determined to be 82.52 min (long) and 9.83 mL/min/kg (low), respectively that is considered a low clearance drug. Slight structural modifications to the 2-methyl propan-2-ol moiety and pyridine ring in drug design could upsurge the ESD metabolic stability. The combined in vitro/in silico method delivers a resource-efficient strategy for early-stage metabolic screening and progressing innovative drug research focused on improving metabolic stability.
Biomed+Chromatogr 2026 ; 40 (1): e70297
