Drug biotransformation samples

Jemal M. et al., 1999. A versatile system of high-flow high performance hquid chromatography with tadem mass spectrometry for rapid direct-injection analysis of plasma samples for quantitation of a /1-lactam drug candidate and its open-ring biotransformation product. Rapid Commun Mass Spectrom 13 1462. 

Despite their reliability, all these techniques are not drug specific they are unable to distinguish the unchanged contrast agent and degradation or biotransformation products containing iodine that are potentially present in the sample. 

Metabolism. JM216 is rapidly biotransformed in vivo with no parent drug being detectable in any of the patient samples examined even as early as 15 min post administration [26]. Six platinum-containing peaks were observed in patient s plasma ultrafiltrate samples [26], Initially, metabolic studies were performed in fresh human plasma incubated with JM216 and... 

Investigations of biotransformation pathways in vivo require the collection and analysis of appropriate biologic samples. The types of sample collected include urine, feces, expired air, blood and/or plasma, bile, milk, saliva, synovial fluid, and tissues. These samples can be divided into two groups 1) those requiring complete collection (e.g., urine and feces) in order to provide quantitative as well as qualitative information on the excretion of the drug and its metabolites and 2) those such as blood and milk that are subsampled at specific times to yield information on the identity and time-related concentrations of the drug and its metabolites that contribute to systemic exposure. Samples of the above types can be obtained from all the common laboratory animals used in biomedical research. In addition, with the exception of bile and tissues, similar samples can usually be obtained from humans without great difficulty. 

Although mass spectra can provide structural informahon, the determinahon of the exact location of biotransformation on a drug molecule is best done by NMR. NMR is considerably more informahon-rich than MS, but less sensihve. This means more material and longer acquisihon times are needed to obtain interpretable data. To determine a metabolite structure, a number of NMR experiments are available. An interpretable one-dimensional (ID) H spectrum for a metabolite can be generated in a few hours from about 1 /rg of metabolite with conventional ambient-temperature 3-mm probes. However, approximately 50 /rg of the same metabolite would be required to acquire a two-dimensional (2D) I I- T mulhbond correlahon data set in a few days. These sample requirements oftentimes exceed the levels generated in most typical metabolism studies. 

Jemal, M. Ouyang, Z. Xia, Y.-Q. Powell, M.L. A Versatile System of High-Flow High Performance Liquid Chromatography with Tandem Mass Spectrometry for Rapid Direct-Injection Analysis of Plasma Samples for Quantitation of a p -Lactam Drug Candidate and its Open Ring Biotransformation Product, Rapid Commun. Mass Spectrom. 13(14), 1462-1471 (1999). 

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