title: Rapid separation of desloratadine and related compounds in solid pharmaceutical formulation using gradient ion-pair chromatography.
abstract: We reported the development of an ion-pair chromatographic method to separate desloratadine and all known related compounds in Clarinex Tablets, which use desloratadine as active pharmaceutical ingredient (API). For the first time, baseline separation for desloratadine and all known related compounds was achieved by utilizing a YMC-Pack Pro C(18) column (150 mm x 4.6 mm I.D., 3 microm particle size, 120A pore size) and a gradient elution method. The mobile phase A contains 3 mM sodium dodecylsulfate (SDS), 15 mM sodium citrate buffer at pH 6.2, and 40 mM sodium sulfate, while the mobile phase B is acetonitrile. Chromsword, an artificial intelligence method development tool, was used to optimize several key chromatographic parameters simultaneously including buffer pH/solvent strength, and temperature/gradient profile. The resolution of desloratadine and desloratadine 3,4-dehydropiperidine derivative, one of the critical pairs was improved by adding 40 mM sodium sulfate. Ultraviolet detection at 267 nm was used to achieve the detection for desloratadine and all compounds. This method has been successfully validated according to ICH guidelines in terms of linearity, accuracy, quantitation limit/detection limit, precision, specificity and robustness. It could be used as a stability indicating method for desloratadine drug substances or drug products that use desloratadine as active pharmaceutical ingredient.
authors.affiliation: Global Quality Services-Analytical Sciences, Schering-Plough Corporation, Union, NJ 07083, USA. jinjian.zheng@spcorp.com
authors.forename: Jinjian
authors.initials: J
authors.lastname: Zheng
authors.forename: Abu M
authors.initials: AM
authors.lastname: Rustum
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D039563:Histamine H1 Antagonists, Non-Sedating / Q000032:analysis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D017336:Loratadine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013607:Tablets; D013696:Temperature
chemical_list: D039563:Histamine H1 Antagonists, Non-Sedating; D012997:Solvents; D013607:Tablets; D017336:Loratadine; C121345:desloratadine