title: Simultaneous Determination of Metformin, Glipizide, Repaglinide, and Glimepiride or Metformin and Pioglitazone by a Validated LC Method: Application in the Presence of Metformin Impurity (1-Cyanoguanidine).
abstract: A rapid, simple, and precise RPLC method was developed for the simultaneous determination of the widely used oral antidiabetic, metformin hydrochloride (MTF), with some commonly coadministered oral antidiabetics from different pharmacological classes-glipizide (GPZ), pioglitazone hydrochloride (PGZ), glimepiride (GLM), and repaglinide (RPG)-in bulk, laboratory-prepared mixtures and pharmaceutical formulations in the presence of metformin-reported impurity [1-cyanoguanidine (CNG)]. Chromatographic separation was achieved using isocratic elution mode with a mobile phase of acetonitrile: 0.02 M potassium dihydrogen phosphate (pH 3.17; 50-50, v/v) flowing through a CN Phenomenex column (Phenosphere Next, 250 × 4.6 mm, 5 μm) at a rate of 1.5 mL/min at ambient temperature. UV detection was carried out at 220 nm. The method was validated according to International Conference on Harmonization guidelines. Linearity, accuracy, and precision were satisfactory for concentration ranges: 0.175-350 μg/mL for MTF, 0.0525-105 μg/mL for GPZ, 0.125-250 μg/mL for PGZ, and 0.05-100 μg/mL for GLM and RPG. Correlation coefficients were >0.99 for all analytes. LOQs were 0.009 μg/mL for MTF, 0.009 μg/mL for GPZ, 0.04 μg/mL for GLM, 0.124 μg/mL for PGZ, and 0.044 μg/mL for RPG. The developed method is specific, accurate, and suitable for the QC and routine analysis of the cited drugs in their pharmaceutical products.
authors.affiliation: Cairo University, Faculty of Pharmacy, Pharmaceutical Chemistry Department, Kasr El-Aini St, Cairo 11562, Egypt.
authors.forename: Asmaa A
authors.initials: AA
authors.lastname: El-Zaher
authors.affiliation: Cairo University, Faculty of Pharmacy, Pharmaceutical Chemistry Department, Kasr El-Aini St, Cairo 11562, Egypt.
authors.forename: Ehab F
authors.initials: EF
authors.lastname: Elkady
authors.affiliation: National Organization for Drug Control and Research (NODCAR), Giza 35521, Egypt.
authors.forename: Hanan M
authors.initials: HM
authors.lastname: Elwy
authors.affiliation: National Organization for Drug Control and Research (NODCAR), Giza 35521, Egypt.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Saleh
mesh_terms: D002219:Carbamates / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D005913:Glipizide / Q000032:analysis*; D006146:Guanidines / Q000032:analysis*; D007004:Hypoglycemic Agents / Q000032:analysis*; D008687:Metformin / Q000032:analysis*; D000077205:Pioglitazone; D010880:Piperidines / Q000032:analysis*; D013453:Sulfonylurea Compounds / Q000032:analysis*; D045162:Thiazolidinediones / Q000032:analysis*
chemical_list: D002219:Carbamates; D006146:Guanidines; D007004:Hypoglycemic Agents; D010880:Piperidines; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C072379:repaglinide; C057619:glimepiride; D008687:Metformin; C004711:dicyandiamido; D000077205:Pioglitazone; D005913:Glipizide