B'Hymer C, Cheever K L
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Division of Applied Research and Technology, Taft Laboratory C-23, 4676 Columbia Parkway, Cincinnati, OH 45226, USA.
J Chromatogr Sci. 2010 May-Jun;48(5):328-33. doi: 10.1093/chromsci/48.5.328.
An accurate and precise analysis procedure is presented for the detection and quantification of cyclophosphamide (CP), 4-ketocyclophosphamide (4-keto-CP), a primary metabolite of CP, and ifosfamide (IF) in human urine. CP and IF are common antineoplastic drugs used for the treatment of many types of cancer. Workers in the healthcare field, including nurses and pharmacists who interact with or prepare prescriptions for patients, have potential low-level exposure to the parent drugs; therefore, an analysis procedure is needed. The main focus of this procedure is the quantitation of 4-keto-CP because it is a primary metabolite of CP exposure and stable under physiological conditions. Sample preparation consists of liquid-liquid extraction of urine with ethyl acetate, and the analysis consists of reversed-phase high-performance liquid chromatography coupled with tandem mass spectrometry for detection of the analytes. Accuracy and precision of this procedure is demonstrated by means of recovery experiments. Recoveries are between 97-105% of theory for the three target analytes at various concentrations (25, 50, 100, and 375 ng/mL for 4-keto-CP; 1, 2, 4, and 15 ng/mL for CP and IF) with relative standard deviations of 8.4% or less. The limit of detection for this procedure is 1 ng/mL for 4-keto-CP, 0.1 ng/mL for CP, and 0.05 ng/mL for IF in urine.
本文介绍了一种准确、精确的分析方法，用于检测和定量人尿中环磷酰胺（CP）、4-酮环磷酰胺（4-酮-CP，CP的主要代谢产物）和异环磷酰胺（IF）。CP和IF是用于治疗多种癌症的常见抗肿瘤药物。医疗领域的工作人员，包括与患者互动或为患者准备处方的护士和药剂师，有可能低水平接触这些母体药物；因此，需要一种分析方法。该方法的主要重点是定量4-酮-CP，因为它是CP暴露的主要代谢产物，且在生理条件下稳定。样品制备包括用乙酸乙酯对尿液进行液-液萃取，分析包括反相高效液相色谱与串联质谱联用，用于检测分析物。通过回收率实验证明了该方法的准确性和精密度。三种目标分析物在不同浓度下（4-酮-CP为25、50、100和375 ng/mL；CP和IF为1、2、4和15 ng/mL）的回收率在理论值的97-105%之间，相对标准偏差为8.4%或更低。该方法对尿中4-酮-CP的检测限为1 ng/mL，CP为0.1 ng/mL，IF为0.05 ng/mL。
