Development of a new GC-MS/MS method for the determination of metformin in human hair

Diabetes mellitus is one of the most important public health challenges. Metformin (1,1-dimethylbiguanide) represents the "gold standard" for the treatment of diabetes mellitus type 2. Despite its important role in reducing mortality and morbidity in the diabetic population, metformin is associated with an increased risk of stroke. To document exposure to a drug, hair is considered to be the specimen of choice to complement blood and urine, since it provides historical detail of a subject's chronic exposure to drug(s). Measuring hair concentration of metformin can be important for forensic toxicologists investigating criminal poisoning or Munchausen's syndrome by proxy. In clinical toxicology, drug monitoring using hair to document metformin observance has not yet been described. To document the interest of hair analysis for metformin, the authors have developed and validated a method using a gas-chromatography tandem mass spectrometry system and applied it to authentic hair obtained from 9 diabetic patients under daily treatment. The validation procedure demonstrated a LOD an LOQ of 1 and 100 pg/mg, respectively and acceptable linearity, repeatability and reproducibility. The hair of the 9 patients tested positive in the low ng/mg range with concentrations ranging from 0.3 to 3.8 ng/mg. It seems obvious, in comparison with other drugs, that metformin is badly incorporated into hair, as the daily dosage varied from 1 to 3 g. Although limited in the number of subjects, the study allowed to postulate a possible correlation between daily dose and concentration in dark hair, while for light hair no correlation was found.