METABOLISM OF 15-(4'-I-123!IODOPHENYL)PENTADECANOIC ACID (I-123!IPPA) IN THE RAT-HEART - IDENTIFICATION OF NEW METABOLITES BY HIGH-PRESSURE LIQUID-CHROMATOGRAPHY AND FAST-ATOM-BOMBARDMENT MASS-SPECTROMETRY

The metabolism of 15-(4'-iodophenyl)pentadecanoic acid (IPPA) in the h eart muscle is commonly believed to end at 4-iodobenzoic acid as the m ain and final product of beta-oxidation. However, investigation of the metabolic fate of IPPA in Langendorff rat hearts using high pressure liquid chromatography (HPLC) and negative fast atom bombardment mass s pectrometry (FAB-MS) revealed new results. After perfusing isolated mt hearts with I-123!IPPA, metabolites were monitored by HPLC using sim ultaneous detection of gamma-radioactivity and u.v. absorbance. The id entification of HPLC separated metabolites was based on their nominal molecular weights as determined by negative FAB-MS. According to these measurements five catabolites were identified with decreasing concent ration: 3-(4'-iodophenyl)propenoic acid much greater than 3-(4'-iodoph enyl)propanoic acid = 5-(4'-iodophenyl)-3-hydroxypentanoic acid much g reater than 4-iodobenzoic acid. Additionally, an anabolic metabolite w as found exclusively in the lipid ester fraction. From the hydrolysed heart lipids this compound was identified as 11-(4'-iodophenyl)undecan oic acid. Its formation is explained by the action of cytosolic fatty acid synthetase on IPPA catabolites. This metabolic behaviour may be o f importance for the interpretation of sequential heart scintigraphy p erformed with I-123!IPPA.