创新链/学科链/研发链/产业链

新药研发前沿动态 / 医药领域趋势进展

高效液相色谱法同时测定对乙酰氨基酚片中主药、特殊杂质及抑菌剂含量

Simultaneous Determination of Main Drug Substance, Specified Impurities and Preservatives in Paracetamol Tablets by High-Performance Liquid Chromatography

  • 摘要: 目的 提升国家药品质量一致性评价品种对乙酰氨基酚片的质量标准,建立一种同时测定对乙酰氨基酚片中主药、特殊杂质及抑菌剂含量的方法。方法 采用高效液相色谱法(high performance liquid chromatography,HPLC),色谱柱采用Caprisil C18-P(150mm×4.6 mm,5μm),以甲醇-水作为流动相进行梯度洗脱,流速1 mL·min-1,检测波长245 nm,柱温30℃,进样量20μL,采用外标法进行定量分析。结果 通过优化色谱条件,实现了主药(对乙酰氨基酚)、2种特殊杂质(对氨基酚、对氯苯乙酰胺)及3种抑菌剂(羟苯甲酯、羟苯乙酯、羟苯丙酯)的有效分离与准确测定。对乙酰氨基酚、对氨基酚、对氯苯乙酰胺、羟苯甲酯、羟苯乙酯、羟苯丙酯的质量浓度线性范围分别为5.012 5~300.75、0.102 2~4.088、0.040 3~1.008、0.200 4~4.007、0.020 26~0.808 6、0.048 58~0.607 2 mg·L-1r≥0.999 6),检出限浓度分别为0.003 00、0.010 22、0.010 08、0.040 07、0.003 04、0.014 57 mg·L-1,定量限浓度分别为0.010 02、0.040 88、0.040 30、0.100 20、0.010 13、0.048 58 mg·L-1。不同加标水平下的平均回收率为95.50%~108.82%,相对标准偏差(relative standard deviation,RSD)(n=6)为0.13%~4.33%。结论 该方法具有高专属性、高准确度、高效简便等优势,可用于对乙酰氨基酚片主药、特殊杂质及抑菌剂的含量测定,为提升对乙酰氨基酚片质量提供依据。

     

    Abstract: Objective To improve the quality standard of paracetamol tablets, one of the products under the national drug quality consistency evaluation program, this study established a method for the simultaneous determination of the main drug substance, specified impurities, and preservatives in paracetamol tablets. Methods High-performance liquid chromatography(HPLC) was performed using a Caprisil C18-P column(150 mm × 4.6 mm, 5 μm) with methanol-water as the mobile phase for gradient elution at a flow rate of 1 mL·min-1, detection wavelength of 245 nm, column temperature of 30 ℃, and injection volume of 20 μL. The external standard method was used for quantitative analysis. Results The chromatographic conditions were optimized, and the main drug substance(paracetamol), two specified impurities(p-aminophenol and p-chloroacetanilide), as well as three preservatives(methylparaben, ethylparaben and propylparaben) were effectively separated and accurately quantified. The linear ranges of mass concentrations for paracetamol, p-aminophenol, p-chloroacetanilide, methylparaben, ethylparaben, and propylparaben were 5.012 5 ~300.75, 0.102 2 ~ 4.088, 0.040 3 ~ 1.008, 0.200 4 ~ 4.007, 0.020 26 ~ 0.808 6, 0.048 58 ~ 0.607 2 mg·L-1, respectively(r ≥ 0.999 6). The limits of detection were 0.003 00, 0.010 22, 0.010 08, 0.040 07, 0.003 04, and 0.014 57 mg·L-1, and the limits of quantification were 0.010 02, 0.040 88, 0.040 30, 0.100 20, 0.010 13, and 0.048 58 mg·L-1, respectively. The average recoveries at different spiked concentration levels ranged from 95.50% to 108.82%, with relative standard deviation(RSD, n = 6) between 0.13% and 4.33%. Conclusion This method exhibits strong specificity, high accuracy, high efficiency, and simplicity. It can be applied to the simultaneous determination of the main drug substance, specified impurities and preservatives in paracetamol tablets, and provides a basis for improving the quality of paracetamol tablets.

     

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