title: Optimization and validation of liquid chromatography and headspace-gas chromatography based methods for the quantitative determination of capsaicinoids, salicylic acid, glycol monosalicylate, methyl salicylate, ethyl salicylate, camphor and l-menthol in a topical formulation.
abstract: Capsaicinoids, salicylic acid, methyl and ethyl salicylate, glycol monosalicylate, camphor and l-menthol are widely used in topical formulations to relieve local pain. For each separate compound or simple mixtures, quantitative analysis methods are reported. However, for a mixture containing all above mentioned active compounds, no assay methods were found. Due to the differing physicochemical characteristics, two methods were developed and optimized simultaneously. The non-volatile capsaicinoids, salicylic acid and glycol monosalicylate were analyzed with liquid chromatography following liquid-liquid extraction, whereas the volatile compounds were analyzed with static headspace-gas chromatography. For the latter method, liquid paraffin was selected as compatible dilution solvent. The optimized methods were validated in terms of specificity, linearity, accuracy and precision in a range of 80% to 120% of the expected concentrations. For both methods, peaks were well separated without interference of other compounds. Linear relationships were demonstrated with R² values higher than 0.996 for all compounds. Accuracy was assessed by performing replicate recovery experiments with spiked blank samples. Mean recovery values were all between 98% and 102%. Precision was checked at three levels: system repeatability, method precision and intermediate precision. Both methods were found to be acceptably precise at all three levels. Finally, the method was successfully applied to the analysis of some real samples (cutaneous sticks).
authors.affiliation: Laboratory for Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, O&N 2, PO Box 923, Herestraat 49, B-3000 Leuven, Belgium.
authors.forename: Jochen
authors.initials: J
authors.lastname: Pauwels
authors.forename: Ward
authors.initials: W
authors.lastname: D'Autry
authors.forename: Larissa
authors.initials: L
authors.lastname: Van den Bossche
authors.forename: Cédric
authors.initials: C
authors.lastname: Dewever
authors.forename: Michel
authors.initials: M
authors.lastname: Forier
authors.forename: Stephanie
authors.initials: S
authors.lastname: Vandenwaeyenberg
authors.forename: Kris
authors.initials: K
authors.lastname: Wolfs
authors.forename: Jos
authors.initials: J
authors.lastname: Hoogmartens
authors.forename: Ann
authors.initials: A
authors.lastname: Van Schepdael
authors.forename: Erwin
authors.initials: E
authors.lastname: Adams
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000032:analysis*; D002164:Camphor / Q000032:analysis; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000032:analysis*; D002849:Chromatography, Gas / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D059625:Liquid-Liquid Extraction; D008610:Menthol / Q000032:analysis; D009824:Ointments / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012459:Salicylates / Q000032:analysis; D020156:Salicylic Acid / Q000032:analysis; D012680:Sensitivity and Specificity
chemical_list: D018712:Analgesics, Non-Narcotic; D009824:Ointments; D004364:Pharmaceutical Preparations; D012459:Salicylates; D008610:Menthol; C020904:glycol salicylate; C041835:ethyl salicylate; D002164:Camphor; C033069:methyl salicylate; D020156:Salicylic Acid; D002211:Capsaicin; C012906:dihydrocapsaicin