Metformin (dimethylbiguanide) is a biguanide derivative in which two hydrogen atoms at the N1 nitrogen have been substituted with methyl groups. It is the only biguanide derivative currently used in the medicine.

The medical products containing metformin hydrochloride as the active substance have been used in patients with type II diabetes (insulin‑independent), in particular in obese patients who cannot achieve normal blood glucose concentrations despite using a diet. In these patients, the pancreas does not produce a sufficient amount of insulin, or the body does not respond normally to insulin, leading to glucose accumulation in the blood. Metformin hydrochloride increases the body’s susceptibility to insulin and helps to restore its normal use in the body.

There are many medical products containing metformin as the active substance in the pharmaceutical market. An important element of ensuring their safety of use is to monitor the impurities.

The possible impurities in metformin hydrochloride are the following related substances: cyanoguanidine, melamine, (4,6-diamine -1,3,5-triazine-2-yl)guanidine,  N,N-dimethyl-1,3,5- triazine-2,4,6-triamine,  1-methylol biguanidine  and  N-methyl methan amine.

According to the USP monograph for tablets containing metformin hydrochloride as the active substance, only the level of unidentified impurities is specified. Their amount cannot exceed 0.1%, and the sum of all impurities cannot exceed the value of 0.6% at metformin hydrochloride concentration of 5 mg/ml. According to the Ph.Eur. and USP monographs for metformin hydrochloride (substance), only the cyanoguanidine assay and tests for individual unidentified impurities are performed.

The Polish Pharmacopoeia contains no monograph for metformin hydrochloride.

The object of our study was to identify and to quantify the first four of the above‑mentioned impurities (due to the availability of standard substances) in medical products containing metformin hydrochloride, and to determine their limits of detection and quantitation. 

The separation of the impurities was performed using a PARTISPHER SCX column and using a spectrophotometric detector (λ = 218 nm). The mobile phase was 1.7% (m/v) ammonium dihydrogen phosphate water solution, with pH adjusted to 3.1 using 85% orthophosphoric acid.

The proposed method is rapid, sensitive and selective, and it can be used to evaluate those medical products for which the impurity tests are not currently performed, as well as those for which only cyanoguanidine or cyanoguanidine and melamine assays are performed.

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