Abstract：
In the era of precision medicine, there is increasing evidence that conventional cytotoxic agents may be suitable candidates for therapeutic drug monitoring (TDM)- guided drug dosage adjustments and patient\'s tailored personalization of non-selective chemotherapies. To that end, many liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assays have been developed for the quantification of conventional cytotoxic anticancer chemotherapies, that have been comprehensively and critically reviewed. The use of stable isotopically labelled internal standards (IS) of cytotoxic drugs was strikingly uncommon, accounting for only 48 % of the methods found, although their use could possible to suitably circumvent patients\' samples matrix effects variability. Furthermore, this approach would increase the reliability of cytotoxic drug quantification in highly multi-mediated cancer patients with complex fluctuating pathophysiological and clinical conditions. LC-MS/MS assays can accommodate multiplexed analyses of cytotoxic drugs with optimal selectivity and specificity as well as short analytical times and, when using stable-isotopically labelled IS for quantification, provide concentrations measurements with a high degree of certainty. However, there are still organisational, pharmacological, and medical constraints to tackle before TDM of cytotoxic drugs can be more largely adopted in the clinics for contributing to our ever-lasting quest to improve cancer treatment outcomes.
摘要：
在精准医学时代,越来越多的证据表明,常规细胞毒性药物可能是治疗药物监测(TDM)指导的药物剂量调整和患者定制的非选择性化疗个性化的合适候选药物.为此,许多液相色谱-串联质谱（LC-MS/MS）测定已被开发用于定量常规细胞毒性抗癌化疗，经过全面和严格的审查。使用稳定的同位素标记的细胞毒性药物内标（IS）非常罕见，只占发现方法的48%，尽管它们的使用可能适当地规避患者\'样本基质效应变异性。此外，这种方法将提高高度多介导的癌症患者细胞毒性药物定量的可靠性,这些患者具有复杂的病理生理和临床波动.LC-MS/MS测定可以适应细胞毒性药物的多重分析，具有最佳的选择性和特异性以及短的分析时间，当使用稳定同位素标记的IS进行定量时，提供浓度测量具有高度的确定性。然而,仍然有组织，药理学,以及在TDM之前解决细胞毒性药物的医疗限制可以在诊所中更广泛地采用，以促进我们对改善癌症治疗结果的持久追求。
