Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
Molecules. 2023 Jan 11;28(2):746. doi: 10.3390/molecules28020746.
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been widely used in the quantitative analysis of drugs. The ubiquitous concomitant drug scenario in the clinic has spawned a large number of co-analyses based on this technique. However, signal suppression caused by concomitant drugs during electrospray ionization may affect the quantification accuracy of analytes, which has not received enough attention. In this study, metformin (MET) and glyburide (GLY) were co-eluted by the conventional optimization of chromatographic conditions to illustrate the effect of signal suppression caused by the combined drugs on the quantitative analysis. The response of MET was not affected by GLY over the investigated concentration range. However, the GLY signal could be suppressed by about 30% in the presence of MET, affecting its pharmacokinetic analysis in simulated samples. As an attempt to solve the suppression of GLY by co-eluting MET, dilution can alleviate the suppression. However, this method still has limitations due to the sacrifice of sensitivity. The stable isotope-labeled internal standard could play a role in correction and improve the quantitative accuracy of GLY, which was further confirmed in the pharmacokinetic study of simulated samples. This study provided an example model to illustrate the possible effect of clinical drug combination on LC-MS/MS drug quantitative analysis and investigated the effective methods to solve this problem.
液相色谱-串联质谱法（LC-MS/MS）已广泛应用于药物的定量分析。由于临床上普遍存在伴随药物的情况，基于该技术产生了大量的共同分析。然而，电喷雾电离过程中伴随药物引起的信号抑制可能会影响分析物的定量准确性，而这一点尚未得到足够的重视。在本研究中，通过常规优化色谱条件使二甲双胍（MET）和格列本脲（GLY）共洗脱，以说明联合用药引起的信号抑制对定量分析的影响。在所研究的浓度范围内，GLY 的响应不受 MET 的影响。然而，在 MET 的存在下，GLY 的信号可被抑制约 30%，从而影响其在模拟样品中的药代动力学分析。作为解决 MET 共洗脱时 GLY 抑制的一种尝试，稀释可以减轻抑制作用。然而，由于牺牲了灵敏度，这种方法仍然存在局限性。稳定同位素标记的内标可在一定程度上发挥校正作用，提高 GLY 的定量准确性，在模拟样品的药代动力学研究中进一步得到了证实。本研究提供了一个示例模型，说明了临床药物联合用药对 LC-MS/MS 药物定量分析的可能影响，并探讨了解决这一问题的有效方法。
