Objective: To establish a method for the rapid identification of 22 illegally added drugs in foot-use cold compress gel, and to quantify the content of 4 drugs. Methods: Use ultra-performance liquid chromatography-high resolution mass spectrometry/mass spectrometry (UPLC-HRMS/MS) for qualitative analysis. Using Hypersil GOLDTM VANQUISH C18 (2.1 mm×100 mm,1.9 μm) chromatographic column, gradient elution was performed with 10 mmol·L-1 ammonium acetate aqueous solution (A) and methanol (B) as mobile phases, column temperature was 40 ℃, flow rate was 0.2 mmol·L-1, ESI ion source was used, and qualitative analysis was performed by switching between positive and negative scanning modes. By comparing the retention time, parent ion, and fragment ion information of the standards and sample under the same chromatographic and mass spectrometric conditions confirmed the illegal added drugs in the sample and the suitable methods were used for quantitative analysis. Results: After qualitative analysis, it was confirmed that the sample contained 4 illegally added drugs: acetaminophen,chloramphenicol,lidocaine hydrochloride and miconazole nitrate. The concentrations of these 4 drugs ranged 2.542-101.7 μg·mL-1, 1.410-169.161 μg·mL-1, 0.002-0.2 μg·mL-1, 5.184-290.304 μg·mL-1, respectively. The peak areas showed good linear relationships with concentrations, with correlation coefficients of 0.999 9, 0.999 7, 0.999 9 and 0.999 1, respectively. The limits of detection were 0.015, 0.143, 0.001,0.833 μg·mL-1, respectively. At three concentration levels, the recovery rates ranged 98.5%-104.5%, 90.2%-99.4%, 79.5%-84.9%, 102.8%- 104.3%, with the RSD of 0.059%-0.28%, 0.20%-0.49%, 1.2%-3.1%, 0.18%-0.40%, respectively. The contents were 195.05, 264.10, 1.24, 67.00 mg per bottle, respectively. Conclusion: The qualitative method is simple, rapid, and highly accurate, while the quantitative method is specific, precise, accurate, and stable, making it suitable for the rapid identification of 22 illegally added drugs and the quantification of 4 illegal added drugs in foot-use cold compress gel.
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