title: Determination of Ro 14-4767 (Loceryl) by LC using automated column switching with ultraviolet and electrochemical detection.
abstract: Ro 14-4767, Loceryl is a member of a new class of antimycotics, and a number of dosage forms are being developed for its topical application. The active, impurities and its major oxidation products are amenable to ultraviolet detection at wavelengths of approximately 220 nm. As new delivery systems and lower strengths have been developed, it was recognized that a more sensitive detection method may be necessary to support product development. Ro 14-4767, Ro 14-3168 (impurity) and diastereomers are readily oxidized at potentials of 0.8 V (vs Ag/AgCl) at a glassy carbon electrode. Electrochemical detection substantially improved the sensitivity relative to UV detection. However, detection of impurities and oxidation products by either UV or electrochemical detection exhibited interference problems from the cream matrix. Employing column switching eliminated the interference problem from the cream matrix and adding tetrahydrofuran to the mobile phase (acetonitrile and pH 7.0 phosphate buffer) significantly increased the selectivity and sensitivity for both UV and electrochemical detection. The method requires the use of two pumps to continually deliver the mobile phase through both detectors before and after valve switching, preventing the baseline from shifting during a stop in the flow to the electrochemical detector. Quantitative recovery of the active, the potential degradation products, and Ro 14-3168 from a placebo cream using column switching and UV detection has been demonstrated. Utilizing this methodology it is possible to quantitate 0.1% of the formulation label claim for the potential degradation products and Ro 14-3168. Electrochemical detection provides greater selectivity in that only Ro 14-3168, Ro 14-4767 and its diastereomers are detected. However, the sensitivity of detection relative to UV is enhanced. The method is linear in the range of 50 to 150% of the working standard solution for 0.01% and 0.001% active concentration of the cream. The column switching technique can be automated for reproducible assay of a large number of samples.
authors.affiliation: Roche Dermatologics, Formulation Research and Development, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
authors.forename: M A
authors.initials: MA
authors.lastname: Czech
authors.forename: M
authors.initials: M
authors.lastname: Meltzer
authors.forename: J
authors.initials: J
authors.lastname: Mouskountakis
mesh_terms: D000935:Antifungal Agents / Q000032:analysis*; D001331:Automation; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods; D004563:Electrochemistry; D016014:Linear Models; D015394:Molecular Structure; D009025:Morpholines / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000935:Antifungal Agents; D009025:Morpholines; C038974:amorolfine