Improved high-performance liquid chromatography tandem mass spectrometry method for quantification of infliximab in pediatric plasma and its application in therapeutic drug monitoring

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry Pub Date : 2024-07-10 DOI:10.1002/rcm.9865

Boran Yu, Siyao Jin, Jiaqi Han, Xiaona Li, Jiamin Xu, Ning Sun, Liang Sun, Xiaoling Wang, Libo Zhao

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引用次数: 0

Abstract

Rationale

The application of infliximab (IFX) to immune-mediated disease is limited by the significant individual variability and associated clinical nonresponse, emphasizing the importance of therapeutic drug monitoring (TDM). Because of the cross-reactivity, limited linear range, and high costs, the clinical application of the previous reported methods was limited. Here, an improved high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to address the issues.

Methods

This study developed an improved bioanalytical HPLC-MS/MS method coupling nanosurface and molecular-orientation limited proteolysis technology. The commercially available compound P14R was selected as the internal standard. This method was developed with fewer volume of reagents and was thoroughly validated. The validated method was applied to TDM in pediatric inflammatory bowel disease (IBD).

Results

Chromatography was performed using a Shim-pack GISS-HP C₁₈ metal-free column (3 μm, 2.1 × 100 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile at 0.4 mL/min. Detection and quantitation were performed using electrospray ionization (ESI) and multiple reaction monitoring in the positive ion mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect, and stability. The method exhibited a linear dynamic range of 0.3–100 μg/mL, with intra- and inter-day precision and relative errors below 15%. The recovery and matrix effect were measured as 87.28%–89.72% and 41.98%–67.17%, respectively, which were effectively compensated by the internal standard. A total of 32 samples collected from 24 pediatric patients with IBD were analyzed using the validated method, and only 46.9% achieved the reported targeted trough level.

Conclusion

This study developed an improved HPLC-MS/MS method for the quantitative determination of IFX concentration in human plasma. The accurate, reliable, and cost-effective method was validated and utilized in the analysis of clinical samples. The results confirmed the importance of TDM on IFX and the clinical application prospects of the improved method.

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改进的高效液相色谱串联质谱法用于定量检测儿科血浆中的英夫利昔单抗及其在治疗药物监测中的应用。

理由：英夫利昔单抗（IFX）在免疫介导疾病中的应用受限于显著的个体差异和相关的临床无应答，这就强调了治疗药物监测（TDM）的重要性。由于交叉反应、有限的线性范围和高昂的成本，以前报道的方法在临床上的应用受到了限制。为了解决这些问题，本研究开发了一种改进的高效液相色谱串联质谱（HPLC-MS/MS）方法：本研究开发了一种改进的生物分析 HPLC-MS/MS 方法，该方法结合了纳米表面和分子取向限制蛋白水解技术。选择市售化合物 P14R 作为内标物。该方法试剂用量较少，并通过了全面验证。将验证后的方法应用于小儿炎症性肠病（IBD）的TDM：采用 Shim-pack GISS-HP C18 无金属色谱柱（3 μm，2.1 × 100 mm），以 0.1% 甲酸水溶液和乙腈为流动相进行梯度洗脱，流速为 0.4 mL/min。采用电喷雾离子化（ESI）和正离子模式下的多反应监测进行检测和定量。对该方法的选择性、线性、准确度、精密度、回收率、基质效应和稳定性进行了验证。该方法的线性动态范围为 0.3-100 μg/mL，日内和日间精密度和相对误差均低于 15%。方法的回收率为87.28%～89.72%，基质效应为41.98%～67.17%，内标物有效地补偿了回收率和基质效应。使用验证方法分析了从24名儿科IBD患者处采集的32份样本，只有46.9%的样本达到了报告的目标谷值水平：本研究开发了一种改进的 HPLC-MS/MS 方法，用于定量测定人血浆中的 IFX 浓度。该方法准确、可靠、经济高效，已在临床样本分析中得到验证和应用。结果证实了TDM对IFX的重要性以及改进方法的临床应用前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Rapid Communications in Mass Spectrometry 化学-分析化学

CiteScore

4.10

自引率

5.00%

发文量

219

审稿时长

2.6 months

期刊介绍： Rapid Communications in Mass Spectrometry is a journal whose aim is the rapid publication of original research results and ideas on all aspects of the science of gas-phase ions; it covers all the associated scientific disciplines. There is no formal limit on paper length ("rapid" is not synonymous with "brief"), but papers should be of a length that is commensurate with the importance and complexity of the results being reported. Contributions may be theoretical or practical in nature; they may deal with methods, techniques and applications, or with the interpretation of results; they may cover any area in science that depends directly on measurements made upon gaseous ions or that is associated with such measurements.