곽보영 (서울대학교)

곽보영 (서울대학교)

 Boyoung Kwak^1*, Ga-yeong Lee¹ and Joo-Youn Cho¹

¹Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea.

Email: by0324@snu.ac.kr

N-lactoyl-phenylalanine (Lac-Phe) and N-lactoyl-tyrosine (Lac-Tyr) are endogenous metabolites associated with metabolic stress and energy metabolism. However, their accurate quantification is challenging due to endogenous baseline levels. This study aimed to develop and validate an LC-MS/MS method using a surrogate matrix approach and evaluate its applicability in human plasma following metformin administration.

The method was validated according to established bioanalytical guidelines, including assessments of accuracy, precision, carry-over, stability, and reinjection reproducibility. Accuracy was within 80-120% at the LLOQ and 85-115% at all other QC levels. Intra- and inter-day precision (CV) was ≤20% at the LLOQ and ≤15% at other QC levels. Minimal carry-over was observed (4.21% for Lac-Phe, 9.76% for Lac-Tyr), well below the limits of 20% for analytes and 5% for the internal standard. Analyte stability was confirmed under various storage/handling conditions. Reinjection reproducibility met the ±15% criteria.

Application of the validated method to clinical plasma samples demonstrated a significant increase in Lac-Phe and Lac-Tyr concentrations following metformin administration compared with baseline levels. These findings suggest that Lac-Phe and Lac-Tyr may serve as potential pharmacodynamic biomarkers reflecting drug-induced metabolic responses.