GC–MS method for routine analysis of camphor, menthol, methyl salicylate, and thymol in traditional topical products: Addressing compliance and adulteration from Malaysia's National Pharmaceutical Regulatory Agency

Abstract

Topical formulations like liniments, ointments, creams, and patches, commonly used for their therapeutic benefits, often rely on potent active compounds such as camphor, menthol, methyl salicylate, and thymol. However, ensuring the accurate quantification of these compounds is critical for maintaining product safety, efficacy, and consistency. In this study, a gas chromatography–mass spectrometry (GC–MS) method was developed and validated to allow for the simultaneous quantification of these compounds, offering a reliable tool for quality control in traditional medicine products. Eugenol was used as the internal standard, and the samples were extracted using a sonication-assisted solvent extraction technique. Separation was achieved using a BP-624 GC capillary column (30 m × 250 μm × 1.4 μm), with acquisition completed within 16 min. The limit of detection (LOD) and limit of quantification (LOQ) were 1 and 3 μg/mL, respectively. Linearity was established for camphor, menthol, methyl salicylate, and thymol, with r² values of 0.999, 0.998, 0.999, and 0.998, respectively. The method demonstrated accuracy, with recoveries ranging between 96.54 %–103.89 % for camphor, 94.98 %–104.10 % for menthol, 97.53 %–104.02 % for methyl salicylate, and 96.72 %–104.70 % for thymol. Acceptable precision was confirmed, with the percentage of relative standard deviations (%RSD) ranging from 1.88 % to 3.69 %. This method was successfully applied to four distinct product formulations and validated using commercially available traditional products, demonstrating its suitability for routine quality control analysis. Subsequently, it was employed to analyse actual surveillance and complaint samples obtained. The analysis revealed considerable variability in the concentrations of active compounds across different formulations. Notably, three samples exceeded the permissible limits outlined in the Drug Registration Guidance Document (DRGD) established by the National Pharmaceutical Regulatory Agency (NPRA), suggesting potential adulteration and non-compliance with regulatory standards. The development and application of this validated method are therefore significant to ensuring product safety, safeguarding consumers, and enforcing adherence to regulatory requirements.