Quantitative determination of Metformin in human plasma by UPLC-MS/MS and results of a 12-month pilot study.

This pilot investigation utilized ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) to monitor metformin plasma concentrations in patients with type 1 diabetes. The study was conducted on a group of 11 patients. Plasma metformin was measured before treatment and at 2, 4 weeks, and 3, 6, and 12 months after initiation. Method validation was performed according to ICH M10 guidelines. The method demonstrated precision (CV < 11.07%), accuracy (89.78-99.44%), and linearity (r² > 0.98) across three independent validation runs in the 100-3000 ng/ml range. The lowest and highest measured concentrations were 163.2 and 2162.9 ng/ml, respectively, with a mean of 918 ± 616.7 ng/ml. For several patients subtherapeutic metformin levels have been reported, whereas other patients approached potentially excessive levels (> 2000 ng/ml). These findings highlight the variability in metformin exposure and the utility of UPLC-MS/MS for monitoring patient adherence and pharmacokinetics.