Departamento de Química Analítica, Escuela Politécnica Superior, Universidad de Sevilla, C/Virgen de África 7, E-41011 Sevilla, Spain.
Departamento de Medicina Preventiva y Salud Pública, Facultad de Farmacia, Universidad de Granada, E-18071 Granada, Spain.
Molecules. 2022 Nov 23;27(23):8139. doi: 10.3390/molecules27238139.
Platinum-based cytostatic drugs are one of the most widely used cancer treatments. They are excreted via the urinary tract and can reach the environment through wastewater, posing a risk to human health due to their side effects. Four identification and quantification techniques, including liquid chromatography (LC) separation coupled to (i) a diode array ultraviolet (UV(DAD)) (ii), mass spectrometer in single ion monitoring mode (LC-MS) and (iii) multiple reaction monitoring mode (LC-MS/MS) and (iv) derivatization with diethyldithiocarbamate prior to LC-MS/MS analysis, have been optimized and compared for the multiresidue determination of main platinized cytostatic drugs (cisplatin, carboplatin, and oxaliplatin) in urine samples. Parameters that affect the efficiency of the chromatographic separation and analytical determination of different methods (column, mobile phase, wavelength, precursor ions, fragmentor, and product ions) were optimized. Analytical features, such as matrix effect, sensitivity, precision, selectivity, and linearity, were calculated. In terms of selectivity, the derivatization technique was discarded since it was only applicable to the platinated sum. A high dilution of the sample with LC-UV(DAD) was needed to reduce the matrix effect. Overall, the LC-MS/MS method presented the best analytical features (% RSD ≤ 12.8%, R ≥ 0.991, or method-detection limits between 0.01-1 µg mL). The selected method was applied to the quantification of platinized cytostatic drugs in hospital urine samples from oncologic patients.
铂类细胞抑制剂是最广泛使用的癌症治疗药物之一。它们通过尿道排出，并可能通过废水进入环境，由于其副作用，对人类健康构成威胁。本文优化并比较了四种鉴定和定量技术，包括液相色谱（LC）分离与（i）二极管阵列紫外（UV（DAD））（ii）、单离子监测模式下的质谱（LC-MS）和（iii）多反应监测模式（LC-MS/MS）和（iv）二乙基二硫代氨基甲酸盐衍生化前的 LC-MS/MS 分析，用于尿液样品中主要铂类细胞抑制剂（顺铂、卡铂和奥沙利铂）的多残留测定。优化了影响不同方法（柱、流动相、波长、前体离子、碎裂器和产物离子）色谱分离和分析测定效率的参数。计算了分析特性，如基质效应、灵敏度、精密度、选择性和线性。就选择性而言，由于该衍生化技术仅适用于铂的总和，因此该技术被废弃。需要用 LC-UV（DAD）对样品进行高稀释，以降低基质效应。总体而言，LC-MS/MS 方法表现出最佳的分析特性（%RSD≤12.8%，R≥0.991，或方法检测限在 0.01-1μg mL 之间）。该方法已应用于肿瘤患者医院尿液样本中铂类细胞抑制剂的定量。
