目的:建立一种高效液相色谱-示差折光检测器(HPLC-RID)方法检测右美沙芬愈创甘油醚糖浆中蔗糖、葡萄糖和果糖的含量,从含糖量的角度评价该制剂质量。方法:采用氨基键合硅胶为填充剂的Phenomenex NH Luna色谱柱(250 mm × 4.6 mm,3 μm),示差折光检测器,以水-乙腈(25∶75)为流动相,柱温为 40 ℃,流速为1.0 mL·min-1,进样体积为20 μL。结果:在该色谱条件下,果糖、葡萄糖、蔗糖和麦芽糖能得到良好分离。3个目标成分,果糖在1.515~30.3 mg·mL-1,葡萄糖在3.52~70.4 mg·mL-1,蔗糖在4.462~89.240 mg·mL-1与峰面积呈线性关系。加样回收率,果糖为99.6%,葡萄糖为99.3%,蔗糖为101.1%,RSD均小于2.0%。3家企业的共73批次糖浆剂中均未检出麦芽糖,未发现违规投料;14批样品中蔗糖含量低于2020年版《中华人民共和国药典》四部通则0116规定的45%(g·mL-1),不合格率为19.2%。较低pH导致蔗糖降解可能是不合格的原因。结论:该方法稳定、简便,可用于右美沙芬愈创甘油醚糖浆中蔗糖以及其转化糖的含量测定,也可用于麦芽糖违规投料筛查。建议右美沙芬愈创甘油醚糖浆pH控制在4~5,降低蔗糖降解率,稳定药品质量。
Objective: To establish a method for the quantitative analysis of fructose, glucose and sucrose in dextromethorphan hydrobromide and guaifenesin syrup by HPLC with differential refractive index detector (HPLC-RID) and to evaluate the quality of the syrup based on the content of these sugars. Methods: The optimal condition for separation and detection was achieved on a NH2 column with the mobile phase of water-acetonitrile (25∶75). The column temperature was 40 ℃. The flow rate was 1 mL·min-1. And the injection volume was 20 μL. Results: Under the chromatographic conditions, fructose, glucose, sucrose and maltose could be well separated. The linear ranges of fructose, glucose, sucrose were 1.515-30.3 mg·mL-1, 3.52-70.4 mg·mL-1 and 4.462-89.240 mg·mL-1, respectively. The recoveries were 99.3%-101.1%,RSD<2.0%. Seventy-three batches of samples from three manufacturers were inspected. No sucrose adulterated maltose was found. However, fourteen batches of samples contained sucrose less than 45%(g·mL-1), which is the minimum limit of the amount of sucrose in syrup in Chinese Pharmacopoeia. The defective rate was 19.4%. Degradation of sugars at lower pH might be the reason for the disqualification. Conclusion: This stable and simple method could not only be used for the determination of sucrose and its inverted sugars, but also for the screening of maltose illegal feeding. It is suggested to tighten the pH of dextromethorphan hydrobromide and guaifenesin syrup to 4-5. This will reduce the degradation rate of sucrose and stabilize the quality of the drug.
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