By using high-performance liquid chromatography, the in vitro conversion of pentamidine to the corresponding amidoximes (N-hydroxypentamidine and N,N'-dihydroxypentamidine) was studied in supernatants of rat liver homogenate centrifuged at 9,000 x g. The presence of the two amidoxime peaks in chromatograms was confirmed by liquid secondary ion mass spectrometry and by unequivocal synthesis of the suspected metabolites. The metabolic reactions were found to be catalyzed by the cytochrome P-450 system (mixedfunction oxidases). The formation of the monohydroxylated product was found to have a Km of 0.48 mM and a Vmax of 29.50 pmol/min per mg of protein, while the dihydroxylated metabolite had a Km of 0.73 mM and a Vmax of 4.10 pmol/min per mg of protein. N,N'-Dihydroxypentamidine was found to have highly reduced antiprotozoal activity in vitro relative to that of pentamidine, and neither of the hydroxylated metabolites nor pentamidine was found to be significantly mutagenic by the Ames test. Contrary to previous reports, pentamidine is readily metabolized to at least two hydroxylated products, and this conversion may be relevant to the clinical use of the compound and to future drug design.Pentamidine [1,5-di(4-amidinophenoxy)pentane] was syn-

53) Lemieux, R. U.; Bock, K.; Delbaere, L. T. J.; Koto, S.; Rao, V. S. (54) Maggio, B.; Cumar F. A,; Caputto, R.Abstract: Major diagnostic peaks in desorption chemical ionization (D/CI) and fast atom bombardment (FAB) mass spectra of various model synthetic phospholipids and related compounds are reported in conjunction with our ongoing research on marine phospholipids. Similarities and differences with some previous studies are presented. Commercially available or partially synthesized, saturated or unsaturated fatty acid containing phospholipids with different head groups such as choline, ethanolamine, mono-and dimethylethanolamine, serine, and glycerol were investigated. For identification purposes, 1,2-diacetylglycerol, 1,2-diacetyl-sn-glycero-3-phosphocholine, and 1 ,2-dipalmitoyl-sn-glycero-3-phosphocholine-d9 were also prepared and their mass spectral behavior studied. In terms of diagnostically useful fragmentations ammonia proved to be superior to methane as reagent gas for chemical ionization. The use of deuterated ammonia shed light on the nature of several fragmentations. In most cases, both chemical ionization and fast atom bombardment techniques exhibited molecular ions and/or related peaks. Desorption chemical ionization with ammonia provided more information about fatty acyl moieties, while fast atom bombardment gave diagnostic peaks about various head groups. These two techniques thus offer complementary information about the structures of intact phospholipids.Phospholipids, together with sterols, are among the main classes While electron-impact mass spectrometry has proved to be a very powerful technique in the structure elucidation of sterols, difficulties of lipids in the cell membranes of living organisms.

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Previous interpretations of the electron impact mass spectrum of the methyl derivative 3-chloro-4(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) has suggested that the isotope cluster beginning at m/z 199 is due solely to the (M -OCH,) fragment ion. The relative abundance of the ratio among the ions at m/z 199, 201 and 203 deviates, however, from the theoretical ratio of ions in a threechlorine isotope cluster. We bypotbesized that the cluster arises from two distinct pathways and is composed of two fragment ions, each containing three chlorine atoms. Accordingly, we deconvoluted the original cluster at m/z 199 by assuming the presence of one three-chlorine isotope cluster at m/z 199 and another threechlorine cluster at m/z 201. The result was that we obtained good agreement between the calculated and theoretical relative abundances of the ions. The presence of these two fragment ions was confirmed by high-resolution gas chromatographylbigh-resolution mass spectrometry at a resolving power of 20000. The mass spectrum of MX, methyhted with deuterated methanol, showed two fragment ions, one which arose from the loss of -OCD, (m/z 199) and the other from the loss of -0CH (m/z 204). Tandem mass spectrometry of the m/z 229 [ M -11 + fragment ion of the methyl derivative of MX showed a product ion at m/z 201. The fragment ion at m/z 201 is formed by the loss of -H from the molecular ion and the subsequent loss of -CO from the [ M -11 + ion. The ion at m/z 199 originates from the molecular ion.

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