Primary metabolites analysis

In another study, an enantioselective assay for the analysis of the enantiomer composition of monomethyl 4-(2, 3 -dichlorophenyl)-2,6-dimethyl-l,4-dihydropyridine-3,5-dicarboxylic acid on the tBuCQN-CSP was proposed (Rs = 3.4) [49], This chiral carboxylic acid is the synthesis intermediate and the primary metabolite... 

Blood from the external auricular vein was sampled in a heparinized syringe at appropriate intervals after intravenous administration. Plasma was separated by centrifugation and then subjected to the modified HPLC method for DIL reported by Verghese, et al (9). The modification permitted simultaneous analysis of DIL and deAcDIL, the primary metabolite of DIL. 

The analysis of phthalate metabolites has recently become of environmental concern. Primary metabolites of phthalate diesters are monoesters, in which one ester function is hydrolyzed. These monoesters have a carboxylic function that is currently derivatized to avoid adsorption during GC determination. Several derivatization agents have been used to block the free acid group. Methyl-esterification was used by Hashizume et al. and Suzuki et al. Silylation was preferred by Jonsson and Boren,and Jonsson et al. to simultaneously determine the diesters, monoesters and phthalic acid in the same analysis. Wahl et al. performed the analysis of three acid metabolites of... 

Men who were exposed to a mist of a specific type of Finnish white spirits used for washing cars (Pfaffli et al. 1985) had elevated levels of dimethylbenzoic acid, a metabolite of trimethylbenzene, in their urine following the workshift. This study attempted to quantify exposure to white spirits through the analysis of dimethylbenzoic acid isomers, which are easily detected markers. It assumed that being in a mixture does not affect the metabolism of trimethylbenzene or any of the other constituents of Stoddard solvent. The amount excreted was linearly related to the estimated exposure level. The composition of the white spirits in this study included 11% aromatics with 1% trimethylbenzene isomers, which is similar to the compositions of Stoddard solvent used in the United States. A correlation between exposure to 1,2,4-trimethylbenzene, a component of white spirits, at the TLV- TWA (25 ppm), and the urinary concentration of 3,4-dimethylhippuric acid (3,4-DMHA) was reported in ceramics workers (Fukaya et al. 1994). Rats were dosed by gavage with t-butylcyclohexane (800 mg/kg), another component of white spirits, and seven compounds were identified as urinary metabolites (Flenningsen et al. 1987). The primary metabolite was trans-4-t-butylcyclohexanol, with lesser amounts of 2 "-hydroxy-4t-butylcyclohexanol, 2-methyl-2-cyclohexylpropanoic acid, 2 "-hydroxy- 4 "-t-butylcyclohexanol, 2-methyl-2-cyclohexy 1-1,3-propanediol, 2-hydroxy-4-butylcyclohexanol, and Cis-4-t- butylcyclohexanol also being detected. Rats that had a white spirit formulation (690.8 mg/kg) applied to their tails 5 days/week for 6 weeks were reported to have excreted several products (dimethylbenzoic acid isomers) of trimethylbenzene metabolism in their urine. 

Many drugs, such as buspirone, undergo multiple oxidative biotransformation reactions. In cases such as buspirone the secondary metabolites, which are minor metabolites in vitro, are major metabolites in the circulation or excreta in humans and animals because primary metabolites are rapidly converted to secondary metabolites. To determine the formation pathways and structures of secondary or sequential metabolites, a method using metabolite incubation and HPLC MSC MS analysis was developed and demonstrated using buspirone as an example (Zhu, 2002). [ Cjbuspirone was incubated with HLM, and metabolic profiling was carried out using HPLC-MSC. The... 

The % dose (or fraction metabolized) for each metabolite is calculated by summing the % dose calculated for each excretion pathway (urine or feces) of the metabolite and any subsequent secondary metabolites. The % dose for each excretion pathway is calculated by multiplying the percent abundance of a characterized metabolite on a radiometric chromatogram by the total radioactivity present in the evaluated sample (once extraction and column efficiencies have been taken into account). More detailed analysis would be required to calculate the fraction metabolized if secondary metabolites were formed from more than one primary metabolite (Bu et al., 2005, 2006). 

The last two relationships between electroorganic chemistry and natural products, biogenetic reasoning and new chemistry, will be considered in more detail. Emphasis will be placed on natural materials from plants, namely the so-called secondary plant metabolites (alkaloids, steroids, pigments, terpenes, etc.). Furthermore, we will be concerned only with those reactions from which products have been isolated and identified. The electrochemistry of such primary metabolites as purines, pyrimidines, flavins, porphyrins, etc. has been dealt with by Dryhurst ( ), but the work has been centered more on mechanistic analysis than preparative experiments. 

MALDI-MSI has been demonstrated to be a suitable technique in pharmaceutical research for providing information of the distribution of low molecular weight compounds such as drugs and their metabolites within whole-body tissue sections. Important ADME information can be determined by MALDI-MSI analysis of the distribution of drugs and metabolites in whole-body tissue sections taken from animals killed at a range of time points postdose. In this example we applied MALDI-MSI to the localization of a compound and its primary metabolite in whole-body mouse sections. 

Phytotoxic ozone (O3) has a similar increasing trend as CO2 in atmosphere, but it is more variable spatially and appears in much lower concentrations (e.g., in range of 30 ppb-80 ppb). Impact of elevated O3 on plant terpenoids and herbivore performance has not been studied as extensively as CO2. A meta-analysis [28] of recent literature of combined O3 and CO2 effects on plants indicated that O3 alone did not affect primary metabolites, but concentrations of terpenoids were significantly increased by 8% and combination with elevated CO2 intensified O3 impact. Although terpenoids were increased, elevated O3 improved some indices of insect performance such as higher pupal mass and shorter larval development time, but these effects were counteracted by elevated CO2. 

AQC is one of the best precolumn fluorescence derivatization reagents for amino compounds [29]. Currently, MS/MS detection is frequently used for the selective determination of biological substances in complex mixtures. The reagent AQC reacts with primary and secondary amines to form aminoquinoline-labeled compounds via a carbamide linkage. These derivatives are separated by reversed-phase liquid chromatography and can be monitored by electrospray ionization—mass spectrometry. The loss of the aminoquinoline tag occurs readily and can be monitored by MS/MS detection, thus, metabolite analysis of amino compounds can be carried out [35]. 

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