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Fast atom bombardment tandem mass spectrometry of the anti‐parasitic agent pentamidine and its oxygenated metabolites
Author(s) -
van Breemen Richard B.,
Jiang Ou,
Tidwell Richard R.,
Hall James Edwin,
Brewer Thomas G.
Publication year - 1995
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.1190300405
Subject(s) - chemistry , pentamidine , tandem mass spectrometry , fast atom bombardment , mass spectrometry , fragmentation (computing) , collision induced dissociation , protonation , chromatography , mass spectrum , ion , organic chemistry , pneumonia , archaeology , computer science , history , operating system
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.