目的: 建立HPLC方法检测鼻用冷敷凝胶(露)中添加的盐酸萘甲唑啉、盐酸苯海拉明及盐酸利多卡因3个化学药物。建立HPLC-MS/MS法对检出的阳性样品进行确认。方法: 试样采用乙腈提取后,用HPLC法检测,采用外标法定量,考察试验方法学,对市售样品进行检测。对阳性样品采用HPLC-MS/MS法确证。 HPLC方法:采用XTerra RP18(150 mm×4.6 mm,5 μm)色谱柱,以50 mmol·L-1乙酸铵(用乙酸或氨试液调节pH至7.8)-乙腈(72∶28)为流动相,流速1.0 mL·min-1,检测波长230 nm;LC-MS/MS方法:采用BEH C18(100 mm×2.1 mm,1.7 μm)色谱柱,以0.1%甲酸水溶液-0.1%甲酸乙腈溶液为流动相,梯度洗脱,柱温40 ℃,流速0.4 mL·min-1;电喷雾电离源(ESI),正离子模式下多反应监测(MRM)。结果: 方法学考察试验表明,盐酸萘甲唑啉、盐酸苯海拉明和盐酸利多卡因的检测限分别为2.4、50和50 ng·mL-1,回收率为93.9%~104.6%,在10~200 μg·mL-1范围内,线性关系良好(r>0.999 0)。对市售的42批样品进行检测,总体检出率达70%(36/42),其中34批检出盐酸萘甲唑啉,2批同时检出盐酸苯海拉明和盐酸利多卡因,存在较大的安全风险。结论: 方法专属性强,灵敏度高,操作简单,准确可靠,可用于鼻用冷敷凝胶(露)中盐酸萘甲唑啉、盐酸苯海拉明及盐酸利多卡因的定性及定量检测。
Objective: To develop an HPLC method for determination of naphazoline hydrochloride,diphenhydram hydrochloride and lidocaine hydrochloride added in nasal cold compress gel (dew),and to establish an HPLC-triple quadrupole mass spectrometry (HPLC-MS) method to confirm the positive samples. Methods: The samples were extracted with acetonitrile,detected by high performance liquidchromatography, quantified by external standard method and confirmed by HPLC-MS. The separation was performed on a XTerra RP18 (150 mm×4.6 mm, 5 μm) column with the mobile phase consisting of 50 mmol·L-1 ammonium acetate (the pH value was adjusted to 7.8 with acetic acid or ammonia solution)-acetonitrile (72∶28) at the flow rate of 1.0 mL·min-1 and the detection wavelength was 230 nm. The analysis was performed on a BEH C18 (100 mm×2.1 mm,1.7 μm) column with a gradient elution of 0.1% formic acid aqueous solution-0.1% formic acid acetonitrile solution. The column temperature was set at 40 ℃ and the flow rate was 0.4 mL·min-1. Electrospray ionization source was applied and operated in positive electrospray ionization and the multiple reaction monitoring mode. Results: The method showed the lowest detection concentrations of naphthazoline hydrochloride,diphenhydramine hydrochloride and lidocaine hydrochloride were 2.4 ng·mL-1, 50 ng·mL-1 and 50 ng·mL-1. The sample recoveries ranged from 93.9% to 104.6%. Good linearities were found in the concentration range of 10-200 μg·mL-1(r>0.999 0). A total of 42 batches of samples were detected and the total positive rate was 70% (36/42). Naphthazoline hydrochloride were found in 34 batches. Diphenhydramine hydrochloride and lidocaine hydrochloride were found in 2 batches simultaneously. Conclusion: The established method is specific, sensitive, simple, accurate and reliable. It can be used for the qualitative and quantitative determination of naphthazoline hydrochloride,diphenhydramine hydrochloride and lidocaine hydrochloride in nasal cold compress gel (dew).
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