Main Acid Metabolite Research Articles

Influence of Metalaxyl and CGA 62828 Adsorption on the Leaching Behavior of Metal‐Contaminated Soils

AbstractPesticides’ degradation in the environment affects their persistence and their environmental impact. In this study, batch experiments are performed to investigate 1) the adsorption of a fungicide, metalaxyl, and its main acid metabolite (CGA 62828) onto the surface of two different soils collected in the metal‐contaminated bay of an industrial area and 2) the influence of these two molecules on the leaching of soluble bases, iron and zinc, from the studied soils. In ultrapure water, adsorption isotherms show that the amount of CGA 62828 adsorbed by the soil particles are higher than the amount of metalaxyl. Furthermore, higher amount of these two molecules are adsorbed at a slower rate by the well‐drained soil in comparison with the more polluted saline anthroposol. In contrary to metalaxyl, CGA 62828 favors the release of the bases K, Na, and Ca by the saline soil in contact with ultrapure water. CGA 62828 also tends to limit the Fe and Zn release which are favored in the presence of metalaxyl. The composition of the local tap water did not significantly influence the adsorbed quantities of metalaxyl and CGA 62828 despite its impact on the Fe and Zn leaching.

Absorption, Distribution, Metabolism, and in Vitro Digestion of Beta-Cypermethrin in Laying Hens.

Beta-cypermethrin (beta-CP), an important pyrethroid insecticide, and its main acid metabolites are frequently detected in human samples. Because beta-CP may pose some risk to human health, we studied dynamics and residues of beta-CP and its metabolites in hen egg, droppings, blood, and 15 other tissues after continuous exposure. A digestive model was then used to study beta-CP's digestive fate. Beta-CP and its metabolites significantly accumulated in tissues with high lipid contents and were readily transferred to eggs. Beta-CP was mainly metabolized into acid metabolites that accumulated in egg and edible tissues of laying hens, suggesting that humans may be exposed to beta-CP acid metabolites through food.

Determination of progabide and its main acid metabolite in biological fluids using high-performance liquid chromatography and electrochemical detection. Application to the measurement of blood/plasma partition ratio.

A method for the measurement in plasma, blood and urine of progabide, its main acid metabolite, and the corresponding benzophenone is described. This assay allows the determination of progabide and its acid metabolite for therapeutic drug monitoring, and with a minimum detectable concentration of 1-10 ng/ml for progabide and its acid metabolite, it is sensitive enough for pharmacokinetic studies. Progabide and its metabolites are extracted from biological samples with toluene at pH 4.5. Following reduction of the imine bond with sodium borohydride, the reduced drugs are back-extracted into an aqueous phase at acid pH and reextracted by diethyl ether at alkaline pH. Progabide, its acid metabolite and the benzophenone are separated by high-performance liquid chromatography using a 3-micron ODS column with a quaternary solvent mixture of methanol-acetonitrile-phosphate buffer (0.033 M, pH 5.5)-sodium chloride (1.5 M) (30:30:40:9, v/v), and detected electrochemically at a potential of +850 mV vs. an Ag/AgCl electrode. Antiepileptic drugs like carbamazepine, carbamazepine epoxide, phenytoin, valproic acid and ethosuximide do not interfere with the assay. Blood/plasma partition ratios of 0.69 and 0.55 for progabide and its acid metabolite, respectively, indicate that the former but not the latter is present in red blood cells.

Plasma pharmacokinetics and metabolism of the benzodiazepine antagonist [11C] Ro 15-1788 (flumazenil) in baboon and human during positron emission tomography studies.

Flumazenil is a specific antagonist of the central benzodiazepine receptor (CBZR). Labelled with 11C, this compound is the reference radioligand for positron emission tomography (PET) study of the CBZR in humans and primates. The time-course of [11C]-flumazenil radioactivity and its main acid metabolite [11C] Ro 15-3890 were reconstructed from the time-course of total radioactivity in plasma after administration with high or low SRA in primates and humans, applying an extraction procedure validated by TLC. The measured pharmacokinetics of [11C]-flumazenil (T1/2 beta = 45.1 +/- 12.3 min, T1/2 alpha = 1.5 +/- 1.5 min; K = 0.14 +/- 0.14 min-1; Vd area = 44.0 +/- 17.0 l; Clp = 40.0 +/- 8.5 l/h) exhibited a very rapid distribution phase followed by fast elimination, with a large volume of distribution; these results were confirmed by HPLC determinations and agree with previously published data on unlabelled flumazenil. Pharmacokinetics of [11C] Ro 15-3890 acid metabolite show that high drug concentrations in the blood are promptly achieved (kf = 0.13 +/- 0.004 min-1), with a very rapid elimination half-life (T1/2m = 4.47 +/- 1.31 min) comparable to that of [11C]-flumazenil. The percentage metabolization of parent compound to the acid [11C] Ro 15-3890 was constant from the 15th minute and was significantly higher in man compared to the monkey. This percentage was increased by prior eating. The other putative metabolites, i.e. labelled [11C] Ro 15-4965 and unlabelled Ro 15-5528, were never observed at detectable concentrations with TLC and HPLC in rabbit, baboon and human blood samples. This pharmacokinetic study of plasma flumazenil may be useful to implement a dynamic method of CBZR quantification using PET and for analysis of pharmacokinetics in brain tissue.

Determination of progabide and its acid metabolite in biological fluids by high-performance liquid chromatography on silica column with ultraviolet detection

A high-performance liquid chromatographic method has been developed for the determination of progabide and its main acid metabolite in blood, serum and involved a single and rapid extraction of drug and metabolite into toluene from the biological matrix buffered at pH 4.8, evaporation of the organic ph the extracts on a silica column with UV detection. SL 81 0142 was used as internal standard. The method was specific for unchanged drug and metabolite and had a sensitivity of ca. 50 ng/ml of biological fluid for both the compounds. The method was successfully applied to the analysis of progabide and its metabolite in biological fluids of patients administered orally with progabide for clinical pharmacokinetic studies and drug monitoring.

Determination of progabide and its main acid metabolite in biological fluids using high-performance liquid chromatography and electrochemical detection: Application to the measurement of blood/plasma partition ratio

A method for the measurement in plasma, blood and urine of progabide, its main acid metabolite, and the corresponding benzophenone is described. This assay allows the determination of progabide and its acid metabolite for therapeutic drug monitoring, and with a minimum detectable concentration of 1–10 ng/ml for progabide and its acid metabolite, it is sensitive enough for pharmacokinetic studies. Progabide and its metabolites are extracted from biological samples with toluene at pH 4.5. Following reduction of the imine bond with sodium borohydride, the reduced drugs are back-extracted into an aqueous phase at acid pH and reextracted by diethyl ether at alkaline pH. Progabide, its acid metabolite and the benzophenone are separated by high-performance liquid chromatography using a 3-μm ODS column with a quaternary solvent mixture of methanol-acetonitrile-phosphate buffer (0.033 M, pH 5.5)—sodium chloride (1.5 M) (30:30:40:9, v/v), and detected electrochemically at a potential of +850 mV vs. an Ag/AgCl electrode. Antiepileptic drugs like carbamazepine, carbamazepine epoxide, phenytoin, valproic acid and ethosuximide do not interfere with the assay. Blood/plasma partition ratios of 0.69 and 0.55 for progabide and its acid metabolite, respectively, indicate that the former but not the latter is present in red blood cells.

Determination of antrafenine and its main acid metabolite, 2-{[7-(trifluoromethyl)-4-quinolinyl]amino}-benzoic acid, in biological fluids using high-performance liquid chromatography with large volume automatic injection and gas—liquid chromatography with derivative formation

Specific and sensitive analytical methods have been developed for the measurement of antrafenine and its main acid metabolite, 2-{[7-(trifluoromethyl)-4-quinolinyl]amino} benzoic acid (FQB), at therapeutic concentrations in plasma and urine. Following the addition of internal standards (the methyl ester of FQB and 2-{[8-(trifluoromethyl)-4-quinolinyl]amino}benzoic acid) the parent drug and the metabolite were extracted from biological material with diethyl ether at a weakly acid pH. Drug extracts were evaporated to dryness prior to chromatographic analysis. Antrafenine was measured by high-performance liquid chromatography using a Spherisorb 5-μm ODS column with acetonitrile—0.1 M sodium acetate as the mobile phase. Samples were injected automatically using a 500-μl injection loop. The detector wavelength was 353 nm corresponding to the maximum UV absorption of both drug and internal standard. The coefficient of variation (C.V.) for the determination of antrafenine concentrations between 5 and 250 ng/ml ranged between 24 and 3%, respectively. The acid metabolite of antranine was measured by gas—liquid chromatography with electron-capture detection using a 1-m column packed with 3% OV-225 on Gas-Chrom Q (100–120 mesh) at 240°C and on-column methylation with trimethylphenyl ammonium hydroxide. The C.V. of the methd for the analysis of metabolite concentrations between 10 and 500 ng/ml ranged between 3 and 9%, respectively.

A study of the conversion of cholesterol to bile acids by the use of a fistulated bile duct

A method for the surgical preparation of a bile fistula in the sculpin Myoxocephalus quadricornis is presented. This model was used in demonstrating the conversion of 14C‐cholesterol into bile acids. The main acid metabolite was cholic acid and the presence of dihydroxy bile acids was also demonstrated. The amount of labelled compounds which was recovered in the bile was small both in case of parenteral administration to fistulated sculpins and after peroral administration to intact animals. This may be attributable to slow metabolism at the low ambient temperature these animals require to survive.

The active transport of 5-hydroxyindol-3-ylacetic acid and 3-methoxy-4-hydroxyphenylacetic acid from a recirculatory perfusion system of the cerebral ventricles of the unanaesthetized dog.

1. An operation on dogs for the implantation of guide tubes to the lateral ventricle and cisterna magna and a method whereby the ventricular space can be repeatedly perfused in conscious and unrestrained animals are described.2. The characteristics of a recirculatory perfusion system were examined and the bulk formation and absorption of cerebrospinal fluid and the volume of the ventricular space perfused were derived from the concentrations achieved during the infusion of inulin into the system.3. 5-hydroxyindol-3-ylacetic acid (5-HIAA), the acid metabolite of 5-hydroxytryptamine, and 3-methoxy-4-hydroxyphenylacetic acid (HVA), the main acid metabolite of dopamine, were demonstrated to be mainly removed from cerebrospinal fluid (c.s.f.) by an active transport system localized in the region of the fourth ventricle.4. It was possible to inhibit the active transport of these acids from cerebrospinal fluid by pre-treating the dogs with probenecid.