Shockcor J P, Unger S E, Savina P, Nicholson J K, Lindon J C
Drug Metabolism and Pharmacokinetics, DuPont Pharmaceuticals Company, Newark, DE 19714, USA.
J Chromatogr B Biomed Sci Appl. 2000 Oct 1;748(1):269-79. doi: 10.1016/s0378-4347(00)00360-1.
The human in vivo metabolism of the HIV-1 reverse transcriptase inhibitor 5-chloro-1-(2',3'-dideoxy-3'-fluoro-erythro-pentofuranosyl)uracil (BW935U83) was studied using 19F NMR spectroscopy, directly coupled LC-NMR and LC-NMR-MS. The number and relative proportions of the drug metabolites were obtained from 19F NMR spectra of whole human urine. The novel use of the continuous-flow 19F detected LC-NMR experiment yielded chromatographic retention times and 19F chemical shifts for the parent drug, the glucuronide conjugate of the parent and an early eluting polar metabolite. The parent drug and its glucuronide conjugate were easily characterised by directly coupled 1H LC-NMR spectroscopy and two-dimensional TOCSY experiments. The identification of the second metabolite was achieved using 19F NMR and directly coupled 1H LC-NMR-MS which furnished the molecular weight, and through the use of MS-MS techniques, information on the fragment ions. This species was identified as 3-fluoro-ribolactone.
利用19F核磁共振波谱、直接联用液相色谱-核磁共振波谱以及液相色谱-核磁共振波谱-质谱联用技术，对HIV-1逆转录酶抑制剂5-氯-1-(2',3'-二脱氧-3'-氟-赤式-戊呋喃糖基)尿嘧啶（BW935U83）的人体体内代谢情况进行了研究。药物代谢产物的数量和相对比例是从整个人类尿液的19F核磁共振波谱中获得的。连续流动19F检测液相色谱-核磁共振实验的新应用，给出了母体药物、母体药物的葡萄糖醛酸缀合物以及一种早期洗脱的极性代谢物的色谱保留时间和19F化学位移。母体药物及其葡萄糖醛酸缀合物通过直接联用1H液相色谱-核磁共振波谱和二维全相关谱实验很容易得到表征。第二种代谢物的鉴定是利用19F核磁共振波谱和直接联用1H液相色谱-核磁共振波谱-质谱联用技术完成的，后者提供了分子量信息，并且通过使用串联质谱技术，得到了碎片离子的信息。该物质被鉴定为3-氟-核糖内酯。
