Simultaneous Determination of Cimetidine and Related Compounds in Pharmaceuticals by HPLC on a Porous Graphitic Carbon Column

Abstract

A high-performance liquid chromatographic method has been developed for determination of cimetidine and its main related compounds, 4-hydroxymethyl-5-methylimidazol (MH), N-cyano-N',N''-dimethylguanidine (Carbonate), 1-methyl-3-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfonyl]ethyl]guanidine (Guanidine), 2-cyano-1-methyl-3-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfonyl] (Sulfoxide), and 1-[(methylamino)[[2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfonyl]ethyl]amino]methylene]urea (Amide). Chromatographic separation was achieved on a porous graphitic carbon (PGC) column with a gradient 17:83 to 19:81 (v/v) acetonitrile-0.05 M potassium phosphate buffer containing 0.40% pentane sulfonic acid at pH 2.5. Analysis was performed at a flow-rate of 1 mL min⁻¹ and the detection wavelength was 228 nm. Calibration plots were linear in the concentration ranges 0.25 to 83 µg mL⁻¹ for cimetidine and Carbonate, 0.25 to 75 µg mL⁻¹ for Guanidine, Amide, and Sulfoxide, and 0.25 to 100 µg mL⁻¹ for MH, with correlation coefficients (R²) between 0.9990 and 0.9998. The lowest detectable concentration of cimetidine and Amide was 0.07 µg mL⁻¹; for MH, Carbonate, Guanidine, and Sulfoxide it was 0.06 µg mL⁻¹. Method repeatability (intraday) and reproducibility (interday) was always less than 2% (n=5). The proposed liquid chromatographic method was successfully used for analysis of commercially available cimetidine dosage forms; recoveries were from 99.2 to 100.8%.