title: An HPLC method to evaluate purity of a steroidal drug, loteprednol etabonate.
abstract: Validation of an analytical method for impurities and degradation products in an active pharmaceutical ingredient is important to assessment of quality and safety in a new pharmaceutical product. In the present study, a high-performance liquid chromatographic method was validated to evaluate purity of loteprednol etabonate (LE). LE and its four related substances, major process impurities and degradation products (PJ-90, PJ-91, LE-11-keto and LE-methyl ester) were well resolved using a phenyl-stationary phase under isocratic conditions. Two photo-degradation products were identified as chloromethyl 17alpha-ethoxycarbonyloxy-11beta-hydroxy-5alpha-methyl-2-oxo-19-norandrosta-1(10),3-diene-17beta-carboxylate and chloromethyl 17alpha-ethoxycarbonyloxy-11beta-hydroxy-1-methyl-3-oxo-6(5-->10alpha)-abeo-19-norandrosta-1,4-diene-17beta-carboxylate. A photo-degradation product, chloromethyl 1beta,11beta-epoxy-17alpha-ethoxycarbonyloxy-2-oxo-10alpha-androsta-4-ene-17beta-carboxylate, was not abundant by ultraviolet detector. The risk depending on only ultraviolet detection should be noted. Calibration curves for PJ-90, PJ-91, LE-11-keto and LE-methyl ester showed linearity over the range of 0.05-2.0% levels in LE with correlation coefficient of 0.999. Accuracy (n = 3) at the concentration of 0.5% level in LE for PJ-90, PJ-91, LE-11-keto and LE-methyl ester were 2.0, 2.0, 2.3 and 2.0%, respectively. Intra-day repeatability (n = 6) at the concentration of 0.5% level in LE for PJ-90, PJ-91, LE-11-keto and LE-methyl ester were 1.4, 1.4, 1.8 and 1.4%, respectively. The lower limits of detection for PJ-90, PJ-91, LE-11-keto and LE-methyl ester were 0.002, 0.001, 0.004 and 0.003% levels in LE, respectively.
authors.affiliation: Senju Pharmaceutical Co. Ltd., 2-5-8, Hiranomachi, Chuo-Ku, Osaka 541-0046, Japan. yasueda@senju.co.jp
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yasueda
authors.forename: Masayo
authors.initials: M
authors.lastname: Higashiyama
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Shirasaki
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Inada
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtori
mesh_terms: D000730:Androstadienes / Q000032:analysis*; D000893:Anti-Inflammatory Agents / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006358:Hot Temperature; D008027:Light; D000069559:Loteprednol Etabonate; D015203:Reproducibility of Results; D012996:Solutions; D013314:Stress, Mechanical; D013535:Suspensions; D013607:Tablets
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D012996:Solutions; D013535:Suspensions; D013607:Tablets; D000069559:Loteprednol Etabonate