title: Stability indicating MEKC method for the determination of gliclazide and its specified impurities.
abstract: A stability indicating-micellar electrokinetic chromatography method was developed and validated for the determination of gliclazide (GCZ) and its specified impurities, gliclazide impurities B (GZB) and F (GZF) in bulk and tablets. The analytes were well separated (Rs>2.1) in 5 min using 10mM phosphate buffer (pH 7.0) containing 15 mM sodium dodecyl sulfate on a fused-silica capillary with an effective length of 40 cm and an inner diameter of 50 μm, injection at 50 mbar for 5s, temperature of 25°C, applied voltage of 20 kV and photodiode array detection at 225 nm. The method showed good linearity (r(2)>0.99, in the ranges of 128-192, 20-60 and 10-50 μg/mL for GCZ, GZB and GZF, respectively) and precision (%RSD for intra- and inter-day precision of less than 2.00%, n=3) for all compounds. Accuracy represented as %recovery was between 99.1 and 100.1% with %RSDs of less than 0.59% (n=3). Limits of detection and quantitation were less than 40 and 120 μg/mL, respectively. The method was robust with %RSDs of migration time and peak areas of less than 1.36% (n=9), when buffer and separating voltage were altered around the optimal values. Stress tests showed that GCZ was stable in alkaline hydrolysis both at room and elevated temperature. However, GCZ degraded under acid and neutral hydrolysis and oxidation condition. Elevated temperature and exposure to sunlight accelerated GCZ degradation and formation of GZB and an unknown degradation product. Stability profiles and degradation kinetics of GCZ could be established using the MEKC method. In addition, the method could be used for assay of GCZ in raw material and commercial tablets and results revealed that contents of GCZ in all samples were within the pharmacopeia limit. No degradation products, especially GZB and GZF, were observed in the investigated samples.
authors.affiliation: Bureau of Drug Control, Food and Drug Administration, Nonthaburi 11000, Thailand; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Athiporn
authors.initials: A
authors.lastname: Doomkaew
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Brompoj
authors.initials: B
authors.lastname: Prutthiwanasan
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand; Center of Excellence for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand. Electronic address: leena.sun@mahidol.ac.th.
authors.forename: Leena
authors.initials: L
authors.lastname: Suntornsuk
mesh_terms: D020374:Chromatography, Micellar Electrokinetic Capillary; D004355:Drug Stability; D005907:Gliclazide / Q000031:analogs & derivatives* / Q000032:analysis*; D011208:Powders / Q000032:analysis; D013607:Tablets / Q000032:analysis
chemical_list: D011208:Powders; D013607:Tablets; D005907:Gliclazide
keywords: Gliclazide; Gliclazide impurity B; Gliclazide impurity F; Micellar electrokinetic chromatography; Stability indicating method