Determination of the Antimetabolite Gemcitabine (2′,2′-Difluoro-2′-deoxycytidine) and of 2′,2′-Difluoro-2′-deoxyuridine by 19F Nuclear Magnetic Resonance Spectroscopy

✍ Scribed by H.T. Edzes; G.J. Peters; P. Noordhuis; J.B. Vermorken

• Publisher: Elsevier Science
• Year: 1993
• Tongue: English
• Weight: 483 KB
• Volume: 214
• Category: Article
• ISSN: 0003-2697
• DOI: 10.1006/abio.1993.1451

✦ Synopsis

The analysis of the new antimetabolite 2 ', 2 '-difluoro2 '-deoxycytidine (Gemcitabine, Eli Lilly Corp.) and of its metabolic deamination product, (2^{\prime}, 2^{\prime})-difluoro-2'deoxyuridine, in urine and plasma by means of ({ }^{19} \mathrm{~F}) NMR is described. Both compounds show AB-type NMR spectra which are characterized as a function of (\mathrm{pH}) at a magnetic field strength of 9.4 T. In the physiological pH range the spectra of both compounds are distinct, despite the fact that both compounds have almost identical average ({ }^{19} \mathrm{~F}) shifts. A linear relation between NMR intensity and concentration in urine has been established. The NMR method does not require sample pretreatment and allows for rapid, nondestructive analysis of Gemcitabine concentrations over (0.01 \mathrm{~mm}). Separation of the two compounds in vivo by ({ }^{19} \mathrm{~F}) NMR spectroscopy is difficult to achieve. (\kappa_{\text {c }} 1983) Academic Press, Inc.