Luo F R, Yen T Y, Wyrick S D, Chaney S G
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill 27599, USA.
J Chromatogr B Biomed Sci Appl. 1999 Mar 19;724(2):345-56. doi: 10.1016/s0378-4347(98)00565-9.
A novel single reversed-phase HPLC system was developed for separating oxaliplatin and its biotransformation products formed in rat plasma. The major stable biotransformation products of oxaliplatin formed in rat plasma were identified as Pt(dach)(Cys)2, Pt(dach)(Met) and free dach. The minor biotransformation products Pt(dach)Cl2, Pt(dach)(GSH) and Pt(dach)(GSH)2 could also be resolved from other Pt-dach complexes. Among these biotransformation products, the identification of Pt(dach)(Met) was further confirmed by LC-ESI-MS, and the identification of Pt(dach)(Cys)2, Pt(dach)(GSH), Pt(dach)(GSH)2 and free dach was confirmed by atomic absorption and double isotope labeling. This HPLC technique should prove useful for separating and identifying the biotransformation products of Pt-dach drugs such as oxaliplatin, ormaplatin and Pt(dach)(mal) in biological fluids. This will allow a more complete characterization of the pharmacokinetics and biotransformations of these Pt-dach drugs, which should in turn lead to a better understanding of the mechanisms leading to their toxicity and efficacy.
开发了一种新型的反相高效液相色谱系统，用于分离奥沙利铂及其在大鼠血浆中形成的生物转化产物。在大鼠血浆中形成的奥沙利铂的主要稳定生物转化产物被鉴定为Pt(dach)(Cys)2、Pt(dach)(Met)和游离的dach。次要生物转化产物Pt(dach)Cl2、Pt(dach)(GSH)和Pt(dach)(GSH)2也能与其他Pt-dach配合物分离。在这些生物转化产物中，Pt(dach)(Met)的鉴定通过液相色谱-电喷雾电离质谱进一步得到证实，而Pt(dach)(Cys)2、Pt(dach)(GSH)、Pt(dach)(GSH)2和游离dach的鉴定则通过原子吸收和双同位素标记得到证实。这种高效液相色谱技术对于分离和鉴定生物流体中Pt-dach类药物（如奥沙利铂、奥马铂和Pt(dach)(mal)）的生物转化产物应是有用的。这将有助于更全面地表征这些Pt-dach类药物的药代动力学和生物转化过程，进而有助于更好地理解导致其毒性和疗效的机制。
