Determination of plasma Metformin by a new cation-exchange HPLC technique

• Published in: Therapeutic drug monitoring Vol. 21; no. 3; pp. 330 - 334
• Main Authors: BONFIGLI, A. R, MANFRINI, S, GREGORIO, F, TESTA, R, TESTA, I, DE SIO, G, COPPA, G
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-06-1999
• Subjects: Administration, Oral; Aged; Analysis; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Chromatography, Ion Exchange; Diabetes Mellitus, Type 2 - drug therapy; Female; General pharmacology; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - blood; Male; Medical sciences; Metformin - adverse effects; Metformin - blood; Pharmacology. Drug treatments; Reproducibility of Results; Sensitivity and Specificity; Human; HPLC chromatography; Routine analysis; Metabolism; In vitro; Ion exchange chromatography; Blood plasma; Therapeutic drug monitoring; Hypoglycemic agent; Absorption; Biguanides; Laboratory investigations; Metformin; Pharmacokinetics; Quantitative analysis
• ISSN: 0163-4356; 1536-3694
• DOI: 10.1097/00007691-199906000-00015

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetic patients. This biguanide can induce dangerous complications such as lactic acidosis when its plasma concentration is too high. For this reason, the determination of plasma metformin should always be done during treatment. We developed a new HPLC method, for the routine determination of plasma metformin, with good reliability, rapid execution, and low costs. Sample preparation involved precipitation of the plasma proteins containing the internal standard buformin with a mixture of methanol, zinc sulfate, and ethylene glycol; the diluted supernatant was injected into a cation-exchange column. The mobile phase was potassium dihydrogenphosphate buffer-containing acetonitrile. The eluent was monitored at 236 nm. The calibration curve is linear within the range of 20-4000 ng/mL; the within-day coefficients of variation were less than 2.2% for metformin and 1.5% for buformin; the day-to-day coefficients of variation were less than 2.5% for metformin and 1.9% for buformin. The mean recoveries obtained from supplemented samples were included between 99.4 and 104.2% for metformin. Many characteristics make this method useful and easily accessible to all clinical laboratories equipped with HPLC instrumentation.