Menicatti Marta, Guandalini Luca, Dei Silvia, Floriddia Elisa, Teodori Elisabetta, Traldi Pietro, Bartolucci Gianluca
NEUROFARBA - Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino Sezione Scienze Farmaceutiche e Nutraceutiche, University of Florence, Via U. Schiff 6,, 50019, Sesto Fiorentino, (FI), Italy.
Istituto di Ricerca Pediatrica Città della Speranza, Corso Stati Uniti 4, 35100, Padova, Italy.
Rapid Commun Mass Spectrom. 2016 Feb 15;30(3):423-32. doi: 10.1002/rcm.7453.
A series of drug plasma stability experiments were carried out to evaluate the bioavailability of three multidrug resistance inhibitors. The studied compounds are positional isomers; therefore, a chromatographic separation or taking advantage of specific collisionally activated decomposition pathways, obtained by tandem mass spectrometry (MS/MS) experiments, is necessary in order to resolve them.
A method was developed for quantitative determination of the analytes in plasma using liquid chromatography (LC) coupled with a triple quadrupole mass spectrometer operating in MS/MS mode. Different collisional approaches were employed based on the potentiality of a triple quadrupole system. Aside from the classical product ion spectroscopy, energy-resolved MS/MS experiments and a post-processing mathematical algorithm tool (LEDA) were used to distinguish among different kinds of inhibitors present in the sample batch.
The developed LC/MS/MS method showed precision between 1.8-7.9%, accuracy ranging from 92.8 to 99.9% and limit of detection (LOD) values in the range 1.0-1.4 ng mL(-1) for all the analytes. The evaluation of matrix effects demonstrated that the sample preparation procedure did not affect the ionization efficiency or recovery (matrix effects and recovery larger than 88%). Finally, the LEDA tool was able to differentiate among the isomers, ensuring their proper monitoring.
The proposed LC/MS/MS method was suitable for evaluating the stability of the analytes in plasma samples, although small concentration variations occurred. Furthermore, the investigation on the energetics of fragmentation pathways allowed the better product ions and optimal abundance ratios to be selected for LEDA application into a multi-component analysis. Copyright © 2015 John Wiley & Sons, Ltd.
开展了一系列药物血浆稳定性实验，以评估三种多药耐药抑制剂的生物利用度。所研究的化合物为位置异构体；因此，为了分离它们，需要进行色谱分离或利用串联质谱（MS/MS）实验获得的特定碰撞活化分解途径。
开发了一种使用液相色谱（LC）与以MS/MS模式运行的三重四极杆质谱仪联用，对血浆中的分析物进行定量测定的方法。基于三重四极杆系统的潜力采用了不同的碰撞方法。除了经典的产物离子光谱法外，还使用了能量分辨MS/MS实验和一种后处理数学算法工具（LEDA）来区分样品批次中存在的不同种类抑制剂。
所开发的LC/MS/MS方法对所有分析物的精密度在1.8 - 7.9%之间，准确度在92.8%至99.9%之间，检测限（LOD）值在1.0 - 1.4 ng mL⁻¹范围内。基质效应评估表明，样品制备过程不会影响电离效率或回收率（基质效应和回收率大于88%）。最后，LEDA工具能够区分异构体，确保对其进行适当监测。
所提出的LC/MS/MS方法适用于评估血浆样品中分析物的稳定性，尽管存在小的浓度变化。此外，对碎裂途径能量学的研究使得能够为LEDA在多组分分析中的应用选择更好的产物离子和最佳丰度比。版权所有© 2015约翰威立父子有限公司。
