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用于经皮冠状动脉介入治疗围手术期即时检测血小板糖蛋白IIb/IIIa抑制剂替罗非班的微型质谱分析

Miniature Mass Spectrometry for Point-of-Care Testing the GPIIb/IIIa Inhibitor Tirofiban during Perioperative Period of Percutaneous Coronary Intervention.

作者信息

Zhou Dongchen, Wu Jiahui, Wang Qingcheng, Liu Yong, Wang Shiqi, Zhang Weizong, Zhang Yunfeng, Ding Huizhi, Shao Yunfei, Wang Haixing, Shen Qing

机构信息

Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China.

Laboratory of Food Nutrition and Clinical Research, Zhejiang Gongshang University, Hangzhou 310018, China.

出版信息

ACS Omega. 2024 Dec 10;9(51):50326-50333. doi: 10.1021/acsomega.4c06581. eCollection 2024 Dec 24.

Abstract

Precise administration of tirofiban must be carefully considered to achieve the best treatment efficacy and maximize safety for patients. Herein, a paper spray ionization (PSI) linear ion trap (LIT) portable mass spectrometer (pMS) based point-of-care testing (POCT) technique was developed for on-site sampling, clinical testing, and immediate analysis of tirofiban blood drug concentrations. The results showed that tirofiban formed a significant and stable parent ion peak at / 441.3 by MS1 full scan in positive ion mode, which fragmented into product ions at / 395.4, / 321.3, / 276.3, and / 260.3 through collision-induced dissociation (CID) in MS/MS. To improve ion response, the parameters were optimized to the voltages of ionization 3600 V, ion isolation 1 (ISO1) 8 V, ion isolation 2 (ISO2) 2 V, and collision-induced dissociation (CID) 3 V. This method was validated, and the limit of detection (LOD) and limit of quantification (LOQ) were found to be 10.1 and 33.7 μg·L, respectively. For precision, it had the relative standard deviation (RSD) of interday precision of 4.8 to 6.7% and the RSD of intraday precision of 7.8 to 8.3%. The recovery of the method ranged from 87.5 to 93.4%. Although matrix effects in blood samples had some inhibitory effects on the target signal formation, the method compensated for part of the matrix effects by establishing a matrix-matched calibration curve, which exhibited good linearity with a 2 of 0.9987. Finally, the method was applied to the detection of tirofiban in clinically collected blood samples. Out of 12 samples, ten had tirofiban concentrations between 35.4 and 72.1 μg·L while the remaining two were below the LOQ. The method needs further optimization and validation in the future to improve its sensitivity and stability.

摘要

为实现最佳治疗效果并使患者安全性最大化,必须仔细考虑替罗非班的精确给药。在此,开发了一种基于纸喷雾电离(PSI)线性离子阱(LIT)便携式质谱仪(pMS)的即时检测(POCT)技术,用于现场采样、临床检测以及即时分析替罗非班血药浓度。结果表明,在正离子模式下通过MS1全扫描,替罗非班在m/z 441.3处形成了显著且稳定的母离子峰,该母离子峰在MS/MS中通过碰撞诱导解离(CID)裂解为m/z 395.4、m/z 321.3、m/z 276.3和m/z 260.3的子离子。为提高离子响应,将参数优化为电离电压3600 V、离子隔离1(ISO1)8 V、离子隔离2(ISO2)2 V以及碰撞诱导解离(CID)3 V。该方法经过验证,检测限(LOD)和定量限(LOQ)分别为10.1和33.7 μg·L。在精密度方面,日间精密度的相对标准偏差(RSD)为4.8%至6.7%,日内精密度的RSD为7.8%至8.3%。该方法的回收率在87.5%至93.4%之间。尽管血样中的基质效应会对目标信号形成产生一定抑制作用,但该方法通过建立基质匹配校准曲线补偿了部分基质效应,其线性良好,R²为0.9987。最后,该方法应用于临床采集血样中替罗非班的检测。在12个样本中,10个样本的替罗非班浓度在35.4至72.1 μg·L之间,其余2个样本低于定量限。该方法未来需要进一步优化和验证,以提高其灵敏度和稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ae2/11683618/ff78c53ee3f7/ao4c06581_0001.jpg

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