title: Analysis of mannitol in pharmaceutical formulations using hydrophilic interaction liquid chromatography with evaporative light-scattering detection.
abstract: This study demonstrates the use of hydrophilic interaction liquid chromatography (HILIC) for the separation of both active and inactive ingredients in pharmaceuticals from a single injection. Excipients commonly used in parenteral formulations were separated using a gradient method employing increasing aqueous composition. An evaporative light-scattering detector (ELSD) provided direct detection of inactive excipients and inorganic salts lacking UV chromophores. Analyses of Gemzar parenteral formulations using optimized isocratic HILIC-ELSD method conditions were performed based on retention time screening from the gradient assay. All of the components were efficiently separated using a TSK-Gel Amide 80 column including gemcitabine, mannitol, and sodium cation demonstrating the qualitative capability of the technique. The method was thoroughly validated for mannitol content to access the quantitative potential of the technique. Validation parameters included linearity, accuracy, specificity, solution stability, repeatability, and intermediate precision. Overall, the method described in this report proved to be very robust and represents a novel technique to conveniently separate and detect the active and inactive components in pharmaceuticals both quickly and accurately.
authors.affiliation: Eli Lilly and Company, Pharmaceutical Sciences Research and Development, Lilly Research Laboratories, Indianapolis IN 46285, USA. risley@lilly.com
authors.forename: Donald S
authors.initials: DS
authors.lastname: Risley
authors.forename: Wendy Q
authors.initials: WQ
authors.lastname: Yang
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Peterson
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000032:analysis; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000032:analysis*; D008027:Light; D008353:Mannitol / Q000032:analysis*; D012542:Scattering, Radiation; D012680:Sensitivity and Specificity; D012997:Solvents; D000093542:Gemcitabine
chemical_list: D005079:Excipients; D012997:Solvents; D003841:Deoxycytidine; D008353:Mannitol; D000093542:Gemcitabine