ISSN:
1076-5174
Keywords:
Chemistry
;
Analytical Chemistry and Spectroscopy
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
,
Physics
Notes:
Although pentamidine (1,5-bis(4′-amidinophenoxy)pentane) is currently in use for the treatment of a variety of parasitic infections, including acquired immune deficiency syndrome-related Pneumocystis carinii pneumonia, its metabolism is still under investigation. Positive-ion fast atom bombardment mass spectrometry was used with high-energy collision-activated dissociation (CAD) and linked scanning at constant B/E to obtain tandem mass spectra of protonated molecules of pentamindine and seven synthetic oxygenated derivatives, which are known metabolites of pentamidine. Charge-initiated fragmentation produced abundant fragment ions of m/z 120 and 137 and loss of neutral ammonia from the protonated analyte that characterized the amidinophenoxy group. The structures of isomeric 2-hydroxypentamidine, 3-hydroxypentamidine and N-hydroxypentamidine could be distinguished based on charge-remote fragmentation that produced a series of fragment ions of the pentyl chain and permitted the exact location of the hydroxyl group in each molecule to be determined. Next, tandem mass spectra were obtained and the charge-initiated and charge-remote fragmentation discussed for four other metabolites of pentamidine, including N,N′-dihydroxypentamidine, 5-(4′-amidinophenoxy)pentanoic acid, 5-(4′-amidinophenoxy) pentan-1-ol, and p-hydroxybenzamidine. Finally, tandem mass spectrometry was used to identify pentamidine and three pentamidine metabolites contained in high-performance liquid chromatographic (HPLC) fractions from rat liver perfusate and rat urine following treatment with pentamidine. Pentamidine metabolites identified in rat urine and liver perfusate using mass spectrometry and HPLC retention times included 2-hydroxypentamidine, 3-hydroxypentamidine and 5-(4′-amidinophenoxy)pentanoic acid.
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jms.1190300405
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