Pippalla Sreenivas, Nekkalapudi Arjuna Rao, Komreddy Venugopal Reddy
Sikkim Professional University, Gangtok, Sikkim, India.
Quality Control Department, Ascent Pharmaceuticals Inc, Central Islip, NY, USA.
Biomed Chromatogr. 2024 Sep;38(9):e5944. doi: 10.1002/bmc.5944. Epub 2024 Jul 14.
A quick, simple, sensitive, efficient and stability-indicating reverse-phase ultraperformance liquid chromatographic method for the estimation of propylparaben, methylparaben and sodium benzoate in a pharmaceutical liquid oral formulation was developed. A Waters Acquity UPLC BEH C, 50 × 2.1 mm, 1.7 μm i.d. column was used to perform chromatographic separation with a 0.1% perchloric acid mobile phase used as solvent A and a mixture of 0.1 % perchloric acid and methanol in the ratio 20:80 (v/v), respectively, as solvent B. The experiments were carried out at a flow rate of 0.4 ml/min and the detection wavelength was 240 nm. The compartment temperature of the column was set at 40°C and the injection volume was set at 2 μl. The main aim of the research was to develop a single UPLC assay method for promethazine (active ingredient) and preservatives in the oral solution of promethazine HCl and dextromethorphan HBr that contains promethazine (active ingredient) and methylparaben, propylparaben and sodium benzoate (preservatives). An assay of dextromethorphan HBr was developed and validated by another HPLC method. The drug and preservatives were eluted at retention times of 19.3 min for promethazine HCl, 9.3 min for methylparaben, 18.9 min for propylparaben and 8.9 min for sodium benzoate. Validation of the developed method was carried out as stated by the International Conference on Harmonization guidelines ICH Q2B and under USP<1225>. The analytical parameters verified specificity/selectivity, linearity, accuracy, ruggedness and robustness. The linearity ranges of promethazine HCL, methylparaben, propylparaben and sodium benzoate were 10-100, 10-80, 1.0-8.0 and 10-80 μg/ml, respectively, with a correlation coefficient of active ingredients and preservatives of 1.00. Percentage recoveries of promethazine, propylparaben, methylparaben, and sodium benzoate were 100.0-100.2, 99.0-100.3, 99.5-98.0 and 99.0-100.0%. The validated analytical method proves that the method is specific, precise, linear, accurate, sensitive, rugged and stable, indicating the quantification of the active ingredient and all preservatives in liquid oral formulations.
建立了一种快速、简单、灵敏、高效且具有稳定性指示功能的反相超高效液相色谱法，用于测定液体制剂口服溶液中对羟基苯甲酸丙酯、对羟基苯甲酸甲酯和苯甲酸钠的含量。采用沃特世 Acquity UPLC BEH C18 柱（50×2.1 mm，内径 1.7 μm）进行色谱分离，以 0.1%高氯酸作为流动相 A，以 0.1%高氯酸与甲醇按 20:80（v/v）比例混合的溶液作为流动相 B。实验在流速为 0.4 ml/min 下进行，检测波长为 240 nm。柱温箱温度设定为 40°C，进样体积设定为 2 μl。该研究的主要目的是开发一种单一的超高效液相色谱法，用于测定含有盐酸异丙嗪（活性成分）、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯和苯甲酸钠（防腐剂）的盐酸异丙嗪和氢溴酸右美沙芬口服溶液中异丙嗪（活性成分）和防腐剂的含量。氢溴酸右美沙芬的含量测定采用另一种高效液相色谱法进行开发和验证。药物和防腐剂的保留时间分别为：盐酸异丙嗪 19.3 min、对羟基苯甲酸甲酯 9.3 min、对羟基苯甲酸丙酯 18.9 min、苯甲酸钠 8.9 min。按照国际协调会议（ICH）Q2B 指南及美国药典<1225>的规定对所开发的方法进行验证。验证的分析参数包括特异性/选择性、线性、准确度、耐用性和稳健性。盐酸异丙嗪、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯和苯甲酸钠的线性范围分别为 10 - 100、10 - 80、1.0 - 8.0 和 10 - 80 μg/ml，活性成分和防腐剂的相关系数均为 1.00。异丙嗪、对羟基苯甲酸丙酯、对羟基苯甲酸甲酯和苯甲酸钠的回收率分别为 100.0 - 100.2%、99.0 - 100.3%、99.5 - 98.0%和 99.0 - 100.0%。经过验证的分析方法证明该方法具有特异性、精密性、线性、准确性、灵敏性、耐用性和稳定性，可用于液体制剂口服溶液中活性成分和所有防腐剂的定量分析。
