气相色谱-串联质谱法测定螺旋霉素中的N-亚硝基二甲胺

doi:10.19894/j.issn.1000-0518.200366

摘要/Abstract

摘要： 采用气相色谱-串联质谱法(GC-MS/MS),建立了螺旋霉素原料药中N-亚硝基二甲胺(NDMA)含量的检测方法。样品的制备使用液液萃取法,先将螺旋霉素溶于硫酸溶液,再用二氯甲烷萃取得到待测液。质谱检测使用多反应扫描模式,定量离子对为74.0→44.0,定性离子对为74.0→42.0。在0.25～50 μg/L范围内的NDMA质量浓度与响应呈现良好线性关系,相关系数为0.99998,仪器检测限和定量限分别为0.1260和0.3819 μg/L。低、中和高3个水平下的硫酸溶液加标回收率在100.20%～103.07%,相对标准偏差(RSD)在0.27%～0.72%,螺旋霉素硫酸溶液的加标回收率在103.23%～107.87%,RSD在0.56%～0.64%。方法重复性检测结果RSD为4.25%。螺旋霉素加酸溶解后放置0、2、4和6 h再萃取,检测结果RSD为2.86%。待测溶液放置0～24 h的峰面积RSD为3.14%,NDMA标准品工作液放置0～24 h的峰面积RSD为3.42%。使用该方法在螺旋霉素原料药中检出的NDMA含量均未超标。

关键词: 螺旋霉素, N-亚硝基二甲胺, 三重四极杆质谱, 方法验证

Abstract: The gas chromatography-tandem mass spectrometry (GC-MS/MS) was employed to detect N-nitrosodimethylamine (NDMA) in spiramycin. The liquid-liquid extraction method was used to extract NDMA. The test sample was first dissolved in sulfuric acid; then, dichloromethane was added for extraction, and the substrate filtrate was extracted to obtain the NDMA solution. Data collection was made using the multi reaction monitoring mode. The NDMA quantitative ion pair is 74→44 and the qualitative ion pair is 74→42. Within the range of 0.25～50 μg/L, the NDMA mass concentration and response present a great linear relationship, and the linear-dependence coefficient is 0.99998. The instrument limit of detection and the limit of quantitation are 0.1260 μg/L and 0.3819 μg/L, respectively. Under low, medium and high levels, the adding standard recovery of sulfuric acid solution is within the range of 100.20%~103.07%, and the RSD is within 0.27%~0.72%; for the spiramycin test sample, the adding standard recovery is between 103.23%～107.87%, and the RSD is within 0.56%～0.64%. The repeatability test results show that the RSD is 4.25%. After the test sample is added with sulfuric acid, it is placed for 0, 2, 4, and 6 h before the extraction test, the RSD is 2.86% based on the results. After the spiramycin test sample is placed for 0~24 h, the RSD of peak area is 3.14%; after the NDMA standard working solution is placed for 0~24 h, the RSD of peak area is 3.42%. This method is employed to detect NDMA in spiramycin, and the results are in accord with the demands.

Key words: Spiramycin, N-Nitrosodimethylamine, Triple quadruple mass spectrometry, Method validation

中图分类号:

O657.6

王文华, 马君, 臧文生, 张宏周, 巩玉荣, 戚峰立, 苏济功, 万剑锋, 樊洪凯. 气相色谱-串联质谱法测定螺旋霉素中的N-亚硝基二甲胺[J]. 应用化学, 2021, 38(8): 1007-1013.

WANG Wen-Hua, MA Jun, ZANG Wen-Sheng, ZHANG Hong-Zhou, GONG Yu-Rong, QI Feng-Li, SU Ji-Gong, WAN Jian-Feng, FAN Hong-Kai. Determination of N-Nitrosodimethylamine in Spiramycin by Gas Chromatography-Tandem Mass Spectrometry[J]. Chinese Journal of Applied Chemistry, 2021, 38(8): 1007-1013.

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