乙醇衍生顶空气相色谱测定氢氯噻嗪原料药中微量甲醛和甲酸的含量

目的：开发微量甲醛和甲酸在原料药中的测定方法。方法：本文建立了一种新型便捷的测定氢氯噻嗪原料药中残留甲醛和甲酸的乙醇衍生顶空气相色谱分析方法，并对建立的方法进行分析方法学验证。在本文检测条件下，甲醛被衍生化成二乙氧基甲烷，甲酸被衍生化成甲酸甲酯。结果：甲醛的最低检测限为31 μg·g^-1，最低定量限为100 μg·g^-1，甲醛的回收率在90.0%~110.0%之间，甲醛和二乙氧基甲烷之间的转化率为99.7%；甲酸的最低检测限为30 μg·g^-1，最低定量限为99 μg·g^-1，甲酸的回收率在90.0%~110.0%之间，甲酸和甲酸乙酯之间的转化率为100.5%。氢氯噻嗪原料药在该色谱条件下不干扰测定，使用建立的方法对不同批次的氢氯噻嗪进行检测，均未检出甲酸，甲醛含量在最低定量限水平以下。结论：本方法经方法学验证，适用于氢氯噻嗪原料药中微量甲醛和甲酸的含量控制。

Objective: To develop a method for quantitative analysis of trace amount of formaldehyde and formic acid in drug substance. Methods: A new and convenient ethanol derivative method from headspace gas chromatography was established for quantitative analysis of residual formaldehyde and formic acid in hydrochlorothiazide API. The established method was validated by analytical methodology. Under the present detection condition,formaldehyde was derived into diethylformal,and formic acid was derived into ethyl formate. Results: For formaldehyde,the detection limit was 31 μg·g^-1,the quantification limit was 100 μg·g^-1;the recovery was within 90.0%-110.0%,the percent conversion from formaldehyde to diethylformal was 99.7%. For formic acid,the detection limit was 30 μg·g^-1,the quantification limit was 99 μg·g^-1;the recovery was within 90.0%-110.0%,the percent conversion from formic acid to ethyl formate was 100.5%. There was no interference from hydrochlorothiazide API during analyzation. In different batches of hydrochlorothiazide,formic acid was not detected and formaldehyde was under the quantification limit. Conclusion: This method is fully validated and applicable to quantitative analysis of trace amount of formaldehyde and formic acid in hydrochlorothiazide API for quality control.

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