(met for' min hye'' droe klor' ide).
Imidodicarbonimidic diamide, N,N-dimethyl-, monohydrochloride.
1,1-Dimethylbiguanide monohydrochloride [1115-70-4].
» Metformin Hydrochloride contains not less than 98.5 percent and not more than 101.0 percent of C4H11N5·HCl, calculated on the dried basis.
Packaging and storage Preserve in well-closed containers. Store at room temperature.
USP Reference standards 11
USP Metformin Related Compound A RS
B: It meets the requirements of the tests for Chloride 191.
Loss on drying 731 Dry it at 105 for 5 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method I 231: 0.001%.
Mobile phase Prepare a solution in water, containing 17 g of monobasic ammonium phosphate per L, adjust with phosphoric acid to a pH of 3.0, and mix.
Standard solution Prepare a solution of USP Metformin Related Compound A RS in water having a known concentration of about 0.2 mg per mL. Transfer 1.0 mL of this solution to a 200-mL volumetric flask, dilute with Mobile phase to volume, and mix. [noteMetformin related compound A is 1-cyanoguanidine. ]
Test solution Transfer about 500 mg of Metformin Hydrochloride, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Diluted test solution Transfer 1.0 mL of the Test solution to a 10-mL volumetric flask, dilute with Mobile phase to volume, and mix. Transfer 1.0 mL of this solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Resolution solution Prepare a solution in water containing about 0.25 mg of metformin hydrochloride and about 0.1 mg of melamine per mL. Transfer 1.0 mL of this solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 218-nm detector and a 4.6-mm × 25-cm column containing packing L9. The flow rate is about 1.0 to 1.7 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between melamine and metformin is not less than 10.
Procedure Separately inject equal volumes (about 20 µL) of the Test solution, the Standard solution, and the Diluted test solution into the chromatograph, record the chromatograms for not less than twice the retention time of metformin, and measure the peak areas. Calculate the percentage of metformin related compound A in the portion of Metformin Hydrochloride taken by the formula:
10C/W(rU / rS)in which C is the concentration, in µg per mL, of USP Metformin Related Compound A RS in the Standard solution; W is the weight, in mg, of Metformin Hydrochloride taken to prepare the Test solution; and rU and rS are the metformin related compound A peak responses obtained from the Test solution and the Standard solution, respectively: not more than 0.02% of metformin related compound A is found.
Calculate the percentage of any other impurity in the portion of Metformin Hydrochloride taken by the formula:
0.1(ri / rS)
in which ri is the peak response for an individual impurity obtained from the Test solution; and rS is the metformin peak response obtained from the Diluted test solution: not more than 0.1% of any other impurity is found; and not more than 0.5% of total impurities is found.
Assay [noteTo avoid overheating of the reaction medium, mix thoroughly throughout the titration, and stop the titration immediately after the endpoint has been reached. ] Dissolve about 60 mg of Metformin Hydrochloride, accurately weighed, in 4 mL of anhydrous formic acid. Add 50 mL of acetic anhydride. Titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction (see Titrimetry 541). Each mL of 0.1 N perchloric acid is equivalent to 8.28 mg of C4H11N5·HCl.
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USP35NF30 Page 3829Pharmacopeial Forum: Volume No. 31(4) Page 1092