Canal-Raffin Mireille, Khennoufa Karim, Martinez Béatrice, Goujon Yves, Folch Celia, Ducint Dominique, Titier Karine, Brochard Patrick, Verdun-Esquer Catherine, Molimard Mathieu
Laboratoire de Pharmacologie Clinique et Toxicologie, CHU de Bordeaux, 33076 Bordeaux, France; INSERM U1219, ISPED, Université de Bordeaux, 33076 Bordeaux, France; Service de Médecine du Travail et de Pathologies Professionnelles, CHU de Bordeaux, 33076 Bordeaux, France; Univ. of Bordeaux, 33076 Bordeaux, France.
Laboratoire de Pharmacologie Clinique et Toxicologie, CHU de Bordeaux, 33076 Bordeaux, France.
J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Oct 21. doi: 10.1016/j.jchromb.2016.10.021.
Highly sensitive ESI-LC-MS/MS methods were developed for urinary biological monitoring of occupational exposure to cyclophosphamide (CP), ifosfamide (IF), and methotrexate (MTX), which are hazardous antineoplastic drugs frequently handled by healthcare professionals. Extraction methods consisted of liquid/liquid extraction for simultaneous urinary CP and IF assays, and of solid phase extraction for the urinary MTX assay. A good linearity (r2>0.997), precision (CV<14.6%), and accuracy (bias<9.9%) were achieved for all compounds. The limit of detection (LOD) was 10pg/ml and the lower limit of quantification (LOQ) was 20pg/ml for all three drugs. Applying these methods in routine, more than 116 healthcare professionals occupationally exposed to antineoplastic drugs were monitored and 635 urines were analysed. Eleven healthcare professionals (9.5%) were found to be contaminated to at least one of the three antineoplastic drugs. Among analysed urines, 22 samples were found positives. The measured concentrations ranged from 20.1 to 1850pg/ml and, for six samples, concentrations were at CP trace level, between the LOD and LOQ values (10-20pg/ml). Such efficient analytical tools combining high specificity with high sensitivity are essential for reliable detection and routine biological monitoring of healthcare professionals occupationally exposed to these widely used antineoplastic drugs. These methods allow to monitor the healthcare professionals exposure to antineoplastic drugs in the aim to assess the effectiveness of collective and individual protective measures.
开发了高灵敏度电喷雾电离液相色谱-串联质谱法（ESI-LC-MS/MS），用于职业接触环磷酰胺（CP）、异环磷酰胺（IF）和甲氨蝶呤（MTX）的尿液生物监测，这些都是医护人员经常处理的危险抗肿瘤药物。提取方法包括用于同时检测尿液中CP和IF的液液萃取，以及用于尿液中MTX检测的固相萃取。所有化合物均具有良好的线性（r2>0.997）、精密度（CV<14.6%）和准确度（偏差<9.9%）。三种药物的检测限（LOD）均为10pg/ml，定量下限（LOQ）均为20pg/ml。将这些方法应用于常规检测，对116名以上职业接触抗肿瘤药物的医护人员进行了监测，并分析了635份尿液样本。发现11名医护人员（9.5%）至少被三种抗肿瘤药物中的一种污染。在分析的尿液中，发现22份样本呈阳性。测量浓度范围为20.1至1850pg/ml，有6份样本的浓度处于CP痕量水平，介于LOD和LOQ值之间（10-20pg/ml）。这种将高特异性与高灵敏度相结合的高效分析工具对于可靠检测和对职业接触这些广泛使用的抗肿瘤药物的医护人员进行常规生物监测至关重要。这些方法有助于监测医护人员对抗肿瘤药物的接触情况，以评估集体和个人防护措施的有效性。
