四极杆-线形离子阱串联质谱法测量血清中万古霉素
Determination of Vancomycin in Serum by Quadrupole-Linear Ion Trap Tandem Mass Spectrometry
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摘要: 本研究采用自主研制的QLIT-6610MD液相色谱-串联质谱系统，建立了测量血清中万古霉素的高准确度方法。样品经蛋白沉淀和液液萃取后，进入QLIT-6610MD系统分析。样本中的内源性物质在保留时间内对目标物无干扰。结果表明：在1.56~50.0 mg/L范围内,万古霉素的线性关系良好，相关系数（R2）≥0.99，检出限和定量限分别为0.19、1.56 mg/L，日内和日间精密度范围分别为1.62%~3.82%和2.07%~5.07%，血清样本的加标回收率为95.97%~97.74%，基质效应归一化因子（CV）≤7.60%，样品保存稳定性CV≤4.26%，进样长时稳定性优于2.13%。通过测定低、中、高质控品对方法进行验证，结果均在靶值范围内。采用QLIT-6610MD、AB API4000和YS EXACT 9900MD 3台液相色谱-串联质谱仪测定42例临床血清样本，经过Deming回归、Bland-Altman分析和Pearson相关性分析，结果具有良好的一致性。本研究证明了自主研制的QLIT-6610MD液相色谱-串联质谱系统能够达到三重四极杆质谱仪的定量水平，可为实时临床分析提供一种新型国产仪器方案。Abstract: The demand for accurate mass spectrometry measurement in the field of clinical diagnosis is increasing. In the face of foreign monopoly, our team has developed new technologies and new methods for the selective enrichment of trace targets in complex matrices by ion traps, and has developed a quadrupole-linear ion trap (quadrupole-linear ion trap, Q-LIT) tandem mass spectrometer with independent intellectual property rights and a liquid chromatography tandem mass spectrometry system (model QLIT-6610MD), which have obtained a medical device registration certificate in China. In this study, a home-built Q-LIT liquid chromatography-tandem mass spectrometer QLIT-6610MD was developed to measure vancomycin in serum with high accuracy . After protein precipitation and liquid-liquid extraction, the samples were analyzed by QLIT-6610MD. The endogenous substances in the samples did not interfere with the quantification. The results showed that vancomycin has a good linear relationship of signal intensity vs. concentration in the range of 1.56-50.0 mg/L with the linear correlation coefficient (R2)≥0.99, and the limit of detection and limit of quantitation are 0.19 and 1.56 mg/L, respectively. Intra-day and inter-day precisions are 1.62%-3.82% and 2.07%-5.07%, respectively. The recoveries of vancomycin in serum samples are 95.97%-97.74%. The coefficient of variability (CV) of matrix effect normalization factor is less than 7.60%, CV of sample stability is better than 4.26%, and CV of long interval sample analysis is better than 2.13%. The method was verified by the determination of low, medium and high quality controls, and the results were all within the range of target values. QLIT-6610MD, AB API4000 and YS EXACT 9900MD were used to determine 42 real clinical serum samples. The correlation and consistency of the data were analyzed by Deming regression, Bland-Altman analysis and Pearson correlation analysis. The results showed good consistency among the results obtained by the three spectrometers, indicating that the data of three instruments are comparable, which prove that the home-made QLIT-6610MD can reach the quantitative accuracy of triple quadrupole-mass spectrometer. The instrument can effectively reduce the interference of matrix ions and enhance the capture efficiency of target ions, based on quadrupole-linear ion trap tandem mass spectrometric technique. QLIT-6610MD has great potential to provide a new instrumentation solution for real-time clinical analysis in the future.
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Keywords:
- quadrupole /
- linear ion trap /
- tandem mass spectrometry /
- vancomycin /
- serum
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