Gas chromatography-mass spectrometric method for quantitative determination in human urine of dicarboxylic (dioic) acids produced in the body as a consequence of cholesterol biosynthesis inhibition.
A capillary gas chromatography-mass spectrometric (GC-MS) method in human urine has been developed and validated for the quantitative determination of dicarboxylic acids (dioic acids) which are produced in the body as a consequence of the administration of an inhibitor of the enzyme squalene synthase, which is involved in the biosynthesis of cholesterol. The standards and quality control (QC) samples were prepared by adding dioic acids into human urine. Internal standard (sebacic acid) was added to each urine sample (0.1 ml) and then dried by evaporation under nitrogen. The dried sample was reacted with pentafluorobenzyl (PFB) bromide under conditions that maximized the formation of the di-PFB ester (at the expense of the mono-PFB ester) of the dioic acids. After drying by evaporation, each sample residue was reconstituted in mesitylene and injected into a capillary GC-MS system via a splitless injection. The detection was by negative ion chemical ionization mass spectrometry with selected ion monitoring (SIM) of the [M-PFB]- of the analytes and the internal standard.
Jemal
M
M
Bristol-Myers Squibb, New Brunswick, NJ 08903-0191, USA.
Ouyang
Z
Z
D000080462:Acyclic Monoterpenes; D000924:Anticholesteremic Agents / Q000378:metabolism* / Q000494:pharmacology; D002784:Cholesterol / Q000096:biosynthesis*; D003998:Dicarboxylic Acids / Q000652:urine*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013451:Sulfonic Acids / Q000378:metabolism* / Q000494:pharmacology
D000080462:Acyclic Monoterpenes; D000924:Anticholesteremic Agents; C107094:BMS 187745; D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; D013451:Sulfonic Acids; C037294:2,6-dimethyloctane-1,8-dioic acid; C114197:2,6-dimethyl-2,6-octadiene-1,8-dioic acid; D002784:Cholesterol; D013186:Farnesyl-Diphosphate Farnesyltransferase