目的:建立一种足用冷敷凝露中22种非法添加药物的识别及其中4种药物的含量测定方法。方法:通过高分辨液质联用法(UPLC-HRMS/MS),采用Hypersil GOLDTM VANQUISH C18 (2.1 mm×100 mm,1.9 μm)色谱柱,以10 mmol·L-1乙酸铵的水溶液(A)-甲醇(B)为流动相,进行梯度洗脱,柱温40 ℃,流速0.2 mL·min-1,采用ESI离子源,正负切换扫描模式进行定性分析。以相同质谱-色谱条件下,对照品和样品的保留时间,母离子和碎片离子信息均一致,确认样品中含有的非法添加药物,并使用适当的方法进行定量分析。结果:经过定性分析,确认样品中含有4种非法添加药物:对乙酰氨基酚、氯霉素、盐酸利多卡因、硝酸咪康唑。这4种药物分别在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浓度范围内,峰面积与浓度呈良好的线性关系,线性相关系数分别为 0.999 9、0.999 7、0.999 9、0.999 1;检测限分别为0.015、0.143、0.001、0.833 μg·mL-1;3个浓度水平回收率分别为98.5%~104.5%、90.2%~99.4%、79.5%~84.9%、102.8%~104.3%;RSD分别为0.059%~0.28%、0.20%~0.49%、1.2%~3.1%、0.18%~0.40%;样品中4种药物的含量分别为每瓶195.05、264.10、1.24、67.00 mg。结论:定性方法简便快捷,准确性好,覆盖面广;定量方法专属性、线性、精密度、准确性、重复性和稳定性均良好,适合医疗器械物理降温设备——足用冷敷凝露中22种非法添加药物的快速识别和其中4种非法添加药物的含量测定。
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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