Toxicokinetics,recovery, and metabolism of triclopyr butotyl (ACTP) ester in goats

Toxicokinetic behavior, recovery, and metabolism studies of ACTP ester and its effect on cytochrome P(450) content of liver microsomal pellet were carried out in black Bengal goat after a single intravenous administration of 11.88 mg kg(-1) and consecutive oral administration of 79.22 mg kg(-1) for 7 days. ACTP ester achieved a maximum blood concentration of 42.64 +/- 4.26 microg mL(-1) at 0.08 h after intravenous administration followed by a sharp decline until 0.5 h, and the minimum blood concentration was recorded at 36 h (1.93 +/- 0.14 microg mL(-1)) postdosing. The kinetic behavior of ACTP ester followed a "two-compartment open model". Comparatively shorter alpha (0.81 +/- 0.02 h(-1)) and greater t1/2 (alpha) (0.86 +/- 0.03 h) indicated a slower rate of distribution of ACTP ester in goat. The t1/2(beta)()) (14.83 +/- 1.49 h) and V(d(area)) (0.91 +/- 0.19 L kg(-1)) suggested a longer elimination phase with general distribution in all compartments of the body. The higher T/B and K12/K21 values associated with a lower f(c) value suggested longer persistence in the tissue compartment at higher concentration. The higher Cl(R) compared to Cl(H) indicated the major amount was eliminated by the kidney. Maximum concentration of ACTP ester including its metabolites, triclopyr acid and trichloropyridinol, was excreted through urine at 48 h. The recovery of ACTP ester including metabolites after repeated nontoxic oral dose administration was 70.09%, of which recovery from feces was 4.45%, suggesting the major portion of administered ACTP ester was absorbed through the gastrointestinal tract of the goat. All of the tissues contained ACTP ester and its metabolites. ACTP ester did not alter the cytochrome P(450) content of the liver tissue following repeated nontoxic oral dose administration for 7 days.     

Toxicokinetics, recovery, and metabolism of metamitron in goat

Toxicokinetic behavior and metabolism studies of metamitron and its effect on the cytochrome P(450) content of liver microsomal pellet were carried out in black Bengal goats after a single oral administration at 278 mg kg(-1) and consecutive oral administration of 30 mg kg(-1) for 7 days. Metamitron was detected in the blood sample at 0.08 h (12.0 +/- 0.87 microg mL(-1)), maximum at 4 h (84.3 +/- 8.60 microg mL(-1)) and minimum (14.6 +/- 1.67 microg mL(-1)) at 36 h blood sample after a single oral administration. The absorption rate constant was 0.69 +/- 0.09 h(-1). The Vd(area) (2.00 +/- 0.08 L kg(-1)) and t(1/2)beta (8.98 +/- 0.70 h) values suggested wide distribution and long persistence of the compound in the body. The values of T approximately B (0.80 +/- 0.04), F(c) (0.55 +/- 0.01), Cl(B) (0.15 +/- 0.00 L kg(-1) h(-1)), and K(21) (0.41 +/- 0.03 h(-1)) suggested that metamitron retained in the blood compared to that in the tissue. Maximum concentration of metamitron residue was found in the adrenal gland followed by bile on day 4 of single oral administration. The higher Cl(R) compared to Cl(H) value indicated the excretion of the major portion (34-40%) through urine compared to feces (20-26%). Maximum concentrations of metamitron and its metabolite, deaminometamitron, were excreted through urine and feces at 48 and 24 h samples, respectively. The recovery of metamitron including its metabolite in terms of parent compound varied from 69.3 to 80.1%, of which contribution of metabolite in terms of parent compound varied from 53.1 to 63.0%. Repeated oral administration of metamitron at 30 mg kg(-1) for 7 days caused induction of the cytochrome P(450) content of liver microsomal pellet of goat, suggesting oxidative deamination of metamitron.     

Structural and functional diversity of bacterial community in soil treated with the herbicide napropamide estimated by the DGGE,CLPP and r/K-strategy approaches

Napropamide is one of the most commonly used herbicide in agricultural practice and can exhibit toxic effect to soil microorganisms. Therefore, the main objective of this study was to examine the genetic and functional diversity of microbial communities in soil treated with napropamide at field rate (FR, 2.25 mg kg⁻¹ of soil) and 10 times the FR (10 × FR, 22.5 mg kg⁻¹ of soil) by the denaturing gradient gel electrophoresis (DGGE) and the community level physiological profile (CLPP) methods. In addition, the r/K-strategy approach was used to evaluate the effect of this herbicide on the community structure of the culturable soil bacteria. DGGE patterns revealed that napropamide affected the structure of microbial community; however, the richness (S) and genetic diversity (H) values indicated that the FR dosage of napropamide experienced non-significant changes. In turn, the 10 × FR dosage of herbicide caused significant changes in the S and H values of dominant soil bacteria. DGGE profiles suggest an evolution of bacteria capable of degrading napropamide among indigenous microflora. Analysis of the CLPPs indicated that the catabolic activity of microbial community expressed as AWCD (average well-color development) was temporary positively affected after napropamide application and resulted in an increase of the substrate richness (S_R) as well as functional biodiversity (H) values. Analysis of the bacterial growth strategy revealed that napropamide affected the r- or K-type bacterial classes (ecotypes). In treated-soil samples K-strategists dominated the population, as indicated by the decreased ecophysiological (EP) index. Napropamide significantly affected the physiological state of culturable bacteria and caused a reduction in the rate of colony formation as well as a prolonged time of growth rate. Obtained results indicate that application of napropamide may poses a potential risk for soil functioning.     

Metabolism of metamitron in goat following a single oral administration of a nontoxic dose level: a continued study

Disposition kinetic behavior and metabolism studies of metamitron and its metabolite in terms of the parent compound were carried out in black Bengal goats after a single oral administration of a nontoxic oral dose at 30 mg kg(-1) of body weight. Metamitron was detected in the blood sample at 5 min (2.23 +/- 0.04 microg mL(-1)), maximum at 1 h (3.43 +/- 0.02 microg mL(-1)) and minimum at 12 h (0.41 +/- 0.01 microg mL(-1)), after a single oral administration. Metabolite [3-methyl-6-phenyl-1,2,4-triazin-5(4H)-one] in terms of the parent compound was detected in the blood sample at 5 min (0.47 +/- 0.006 microg mL(-1)), maximum at 6 h (5.12 +/- 0.02 microg mL(-1)) and minimum at 96 h (1.06 +/- 0.016 microg mL(-1)), after a single oral administration. The t(1/2 K) and Cl(B) values of metamitron were 3.63 +/- 0.05 h and 1.36 +/- 0.016 L kg(-1) h(-1), respectively, whereas the t(1/2K)(m) and Cl(B)(m) values of the metabolite were 38.15 +/- 0.37 h and 0.091 +/- 0.001 L kg(-1) h(-1), respectively, which suggested long persistence of the metabolite in blood and tissues of goat. Metamitron was excreted through feces and urine for up to 48 and 72 h, whereas the metabolite was excreted for up to 168 and 144 h, respectively. Metabolite alone contributed to 96 and 67% of combined recovery percentage of metamitron and metabolite against the administered dose in feces and urine of goat, respectively. All of the goat tissues except lung, adrenal gland, ovary, testis, and mammary gland retained the metabolite residue for up to 6 days after administration.     

Metabolism of furametpyr. 2. (14)C excretion, (14)C concentrations in tissues, and amounts of metabolites in rats

14C-Labeled furametpyr [N-(1,3-dihydro-1,1, 3-trimethylisobenzofuran-4-yl)-5-chloro-1, 3-dimethylpyrazole-4-carboxamide, Limber] was dosed to male and female rats at 1 (low dose) and 200 or 300 mg/kg (high dose). Elimination of furametpyr was rapid, and the dosed (14)C was substantially excreted within 7 days (45.5-53.3% in feces, 44.1-53. 8% in urine, and 0.01% in expired air). However, (14)C excretion rate showed sex- and dose-related differences, more rapid in males at low dose. (14)C concentrations in tissues decreased rapidly to generally low levels at 7 days (<0.004 ppm with the low dose and <1. 1 ppm with the high dose). Forty metabolites were detected, and 13 metabolites and 4 glucuronides were identified. A small amount of unchanged furametpyr was detected in feces (0.1-0.5% of the dose). The major metabolites in tissues were N-demethylated metabolites. In a bile study, 52.5-54.2% of the dosed (14)C was rapidly excreted into bile within 2 days. The absorption ratio was estimated to be >93.7% for the low dose (1 mg/kg). Major metabolites in bile were glucuronic acid conjugates of furametpyr hydroxides. On the basis of the results, furametpyr is substantially absorbed from the gastrointestinal tract after oral administration, rapidly distributed to tissues, extensively metabolized, and excreted into urine and bile or feces.     

Metabolism of 7-fluoro-6-(3,4,5,6-tetrahydrophthalimido)-4- (2-propynyl)-2H-1,4-benzoxazin-3(4H)-one (S-53482) in rat. 1. Identification of a sulfonic acid type conjugate

To examine the metabolic fate of 7-fluoro-6-(3,4,5, 6-tetrahydrophthalimido)-4-(2-propynyl)-2H-1,4-benzoxazin-3( 4H)-one (S-53482), rats were given a single oral dose of [phenyl-(14)C]-S-53482 at 1 (low) or 100 (high) mg/kg. The radiocarbon was almost completely eliminated within 7 days after administration in both groups. (14)C recoveries (expressed as percentages relative to the dosed (14)C) in feces and urine were 56-72 and 31-43%, respectively, for the low dose and 78-85 and 13-23%, respectively, for the high dose. S-53482 and seven metabolites were identified in urine and feces. Six of them were purified by several chromatographic techniques and identified by spectroanalyses (NMR and MS). Alcohol derivatives and an acetoanilide derivative were isolated from urine. Three sulfonic acid conjugates having a sulfonic acid group incorporated into the double bond of the 3,4,5,6-tetrahydrophthalimide moiety were isolated from feces. On the basis of the metabolites identified in this study, the metabolic pathways of S-53482 in rats are proposed.     

Metabolism of 7-fluoro-6-(3,4,5,6-tetrahydrophthalimido)-4- (2-propynyl)-2H-1,4-benzoxazin-3(4H)-one (S-53482, flumioxazin) in the rat: II. Identification of reduced metabolites

On single oral administration of (14)C-S-53482 [7-fluoro-6-(3,4,5, 6-tetrahydrophthalimido)-4-(2-propynyl)-2H-1,4-benzoxazin-3( 4H)-one, Flumioxazin] labeled at the 1- and 2-positions of tetrahydrophthaloyl group to rats at 1 (low dose) or 100 (high dose) mg/kg, the radiocarbon was almost completely eliminated within 7 days after administration in both groups with generally very low residual (14)C tissue levels. The predominant excretion route was via the feces. The major fecal and urinary metabolites involved reduction or sulfonic acid addition reactions at the 1,2-double bond of the 3,4,5,6-tetrahydrophthalimide moiety and hydroxylation of the cyclohexene or cyclohexane ring. One urinary and four fecal metabolites were identified using chromatographic techniques and spectroanalyses (NMR and MS). Three of five identified metabolites were unique forms, reduced at the 1,2-double bond of the 3,4,5, 6-tetrahydrophthalimide moiety. On the basis of the metabolites identified in this study, the metabolic pathways of S-53482 in rats are proposed. To specify tissues forming reduced metabolites, an in vitro study was conducted. Reduction was found to take place in red blood cells.     

Metabolism of [(1)(4)C]prometryn in rats.

[(1)(4)C]Prometryn, 2, 4-bis(isopropylamino)-6-(methylthio)-s-triazine, was orally administered to male and female rats at approximately 0.5 and 500 mg/kg; daily urine and feces were collected. After 3 or 7 days rats were sacrificed, and blood and selected tissues were isolated. The urine and feces extracts were characterized for metabolite similarity as well as for metabolite identification. Over 30 metabolites were observed, and of these, 28 were identified mostly by mass spectrometry and/or cochromatography with available reference standards. The metabolism of prometryn was shown to occur by N-demethylation, S-oxidation, S-S dimerization, OH substitution for NH(2) and SCH(3), and conjugation with glutathione or glucuronic acid. Rat liver microsomal incubations of prometryn were conducted and compared to the in vivo metabolism. Both in vivo and in vitro phase I metabolisms of prometryn were similar, with S-oxidation and N-dealkylation predominating. The involvement of cytochrome P-450 and flavin-containing monooxidase in the in vitro metabolism of prometryn was investigated.     

Nature of the residue of [(14)C]Cloransulam-methyl in lactating goats

Two lactating goats were given a daily oral dose of either [UL-aniline-(14)C; AN] or [triazolopyrimidine-7,9-(14)C; TP]cloransulam-methyl for 5 consecutive days. Each animal received a dietary equivalent of approximately 10 mg/kg of test material, approximately 2225 times the realistic maximum dietary exposure for a dairy animal. Milk, urine, and feces samples were collected in the morning and afternoon for each animal. Each goat was sacrificed within 23 h of receiving the last dose, and the liver, kidneys, samples of blood, fat, muscle, and gastrointestinal tract contents, and urine from the bladder were collected. All of these samples were analyzed for (14)C content. Cloransulam-methyl (CM) was rapidly excreted by the animals, with 99.9% of the recovered radioactivity appearing in the urine and feces. Radiochemical analysis showed very low residues, with the highest being in the kidneys at 0.122 and 0. 128 mg equiv of CM/kg (AN and TP labeled compounds, respectively). Radioactive residues were extracted and fractionated from kidney, liver, and milk. Analysis showed approximately 0.066 mg/kg CM in the kidney but <0.003 mg/kg in the liver. Only one metabolite, cloransulam, was identified (in liver, 9.5% of total radioactive residue; 0.005 mg/kg). All other metabolites were present at lower levels. Sulfonanilide bridge cleavage was not a significant degradation route for cloransulam-methyl in ruminants. These data indicated a very low bioaccumulation potential for cloransulam-methyl and its metabolites in ruminants. For a ruminant exposed to anticipated levels of cloransulam-methyl in its diet, parent and metabolites, in total, would not be expected to exceed 50 ng/kg in the kidney and liver.     

Metabolism of [(14)c]chlorantraniliprole in the lactating goat

Metabolism of [(14)C]chlorantraniliprole {3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1- (3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide} was investigated in a lactating goat following seven consecutive daily single oral doses. Each dose was equivalent to 10.4 mg/kg of feed. There was no significant transfer of residues of either chlorantraniliprole or its metabolites into fat, meat, or milk. Chlorantraniliprole and its metabolites accounted for 93.57% of the administered dose and were eliminated primarily in the excreta. Residues in meat, milk, liver, and kidney together accounted for ca. 1.5% of the administered radioactivity. A total of 19 metabolites including 3 glucuronide conjugates and intact chlorantraniliprole were identified in the feces, urine, or tissues by comparison of their HPLC retention times, mass spectral fragments (LC-MS/MS), or multiple reaction monitoring (MRM) transitions to authentic synthesized standards. The major metabolic pathways of [(14)C]chlorantraniliprole in the goat were N-demethylation, methylphenyl hydroxylation, and further oxidation to the carboxylic acid; loss of water from the N-hydroxymethyl group to yield various cyclic metabolites; and hydrolysis of N-methyl amides to form benzoic acid derivatives. Minor metabolic reactions involved cleavage of the amide bridge between the phenyl and heterocyclic rings of chlorantraniliprole.     

Absorption, tissue distribution, excretion, and metabolism of clothianidin in rats

Absorption, distribution, excretion, and metabolism of clothianidin [(E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine] were investigated after a single oral administration of [nitroimino-(14)C]- or [thiazolyl-2-(14)C]clothianidin to male and female rats at a dose of 5 mg/kg of body weight (bw) (low dose) or 250 mg/kg of bw (high dose). The maximum concentration of carbon-14 in blood occurred 2 h after administration of the low oral dose for both labeled clothianidins, and then the concentration of carbon-14 in blood decreased with a half-life of 2.9-4.0 h. The orally administered carbon-14 was rapidly and extensively distributed to all tissues and organs within 2 h after administration, especially to the kidney and liver, but was rapidly and almost completely eliminated from all tissues and organs with no evidence of accumulation. The orally administered carbon-14 was almost completely excreted into urine and feces within 2 days after administration, and approximately 90% of the administered dose was excreted via urine. The major compound in excreta was clothianidin, accounting for >60% of the administered dose. The major metabolic reactions of clothianidin in rats were oxidative demethylation to form N-(2-chlorothiazol-5-ylmethyl)-N'-nitroguanidine and the cleavage of the carbon-nitrogen bond between the thiazolylmethyl moiety and the nitroguanidine moiety. The part of the molecule containing the nitroguanidine moiety was transformed mainly to N-methyl-N'-nitroguanidine, whereas the thiazol moiety was further metabolized to 2-(methylthio)thiazole-5-carboxylic acid. With the exception of the transiently delayed excretion of carbon-14 at the high-dose level, the rates of biokinetics, excretion, distribution, and metabolism of clothianidin were not markedly influenced by dose level and sex.     

Metabolism and distribution of [2,3-(14)C]acrolein in lactating goats

The metabolism and distribution of [2,3-(14)C]acrolein were studied in a lactating goat orally administered 0.82 mg/kg of body weight/day for 5 days. Milk, urine, feces, and expired air were collected. The goat was killed 12 h after the last dose, and edible tissues were collected. The nature of the radioactive residues was determined in milk and tissues. All of the identified metabolites were the result of the incorporation of acrolein into the normal, natural products of intermediary metabolism. There was evidence that the three-carbon unit of acrolein was incorporated intact into glucose, and subsequently lactose, and into glycerol. In the case of other natural products, the incorporation of radioactivity appeared to result from the metabolism of acrolein to smaller molecules followed by incorporation of these metabolites into the normal biosynthetic pathways.     

15N标记羊粪和稻草还田氮素的转化和效应的研究

本工作通过田间微区试验，研究了＾１５Ｎ标记羊粪和稻草单独施用或分别与尿素配合施用作为水稻基肥时，肥料氮的命运及共对水稻产量的影响。     

Oxidative metabolites of the mammalian lignans enterodiol and enterolactone in rat bile and urine

Recent studies have shown that the mammalian lignans enterodiol (END) and enterolactone (ENL) are biotransformed in vitro by hepatic microsomes from rats and humans to various metabolites carrying one additional hydroxy group either at the aromatic or at the aliphatic moiety. To clarify whether these metabolites are also formed in vivo, each lignan was administered intraduodenally at a dose of 10 mg/kg of bw to bile duct-catheterized female Wistar rats and the 6 h bile analyzed by HPLC and GC-MS. With END-dosed rats, three products of aromatic and two of aliphatic monohydroxylation were found, whereas six aromatic and five aliphatic monohydroxylated biliary metabolites were detected after administration of ENL. The metabolites hydroxylated at the aromatic rings were unequivocally identified by comparison with synthetic reference compounds. The structures of the in vivo metabolites arising from aliphatic hydroxylation could not be completely elucidated; they were identical with some of the formerly reported microsomal products according to GC retention times and mass spectra. Significant amounts of most of the metabolites of the mammalian lignans identified in bile were also found in the urine of female rats after oral administration of 10 mg/kg of bw END or ENL and in the urine of female and male Wistar rats after they had been fed a diet containing 5% flaxseed. Thus, the mammalian lignans END and ENL give rise to several hydroxylated metabolites in vivo, which may contribute to the biological effects of these important food constituents.     

Pharmacokinetics of cycloalliin, an organosulfur compound found in garlic and onion, in rats

Cycloalliin, an organosulfur compound found in garlic and onion, has been reported to exert several biological activities and also to remain stable during storage and processing. In this study, we investigated the pharmacokinetics of cycloalliin in rats after intravenous or oral administration. Cycloalliin and its metabolite, (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid, in plasma, urine, feces, and organs was determined by a validated liquid chromatography-mass spectrometry method. When administered intravenously at 50 mg/kg, cycloalliin was rapidly eliminated from blood and excreted into urine, and its total recovery in urine was 97.8% +/- 1.3% in 48 h. After oral administration, cycloalliin appeared rapidly in plasma, with a tmax of 0.47 +/- 0.03 h at 25 mg/kg and 0.67 +/- 0.14 h at 50 mg/kg. Orally administered cycloalliin was distributed in heart, lung, liver, spleen, and especially kidney. The Cmax and AUC0-inf values of cycloalliin at 50 mg/kg were approximately 5 times those at 25 mg/kg. When administered orally at 50 mg/kg, cycloalliin was excreted into urine (17.6% +/- 4.2%) but not feces. However, the total fecal excretion of (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid was 67.3% +/- 5.9% (value corrected for cycloalliin equivalents). In addition, no (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid was detected in plasma (<0.1 microg/mL), and negligible amounts (1.0% +/- 0.3%) were excreted into urine. In in vitro experiments, cycloalliin was reduced to (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid during anaerobic incubation with cecal contents of rats. These data indicated that the low bioavailability (3.73% and 9.65% at 25 and 50 mg/kg, respectively) of cycloalliin was due mainly to reduction to (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid by the intestinal flora and also poor absorption in the upper gastrointestinal tract. These findings are helpful for understanding the biological effects of cycloalliin.     

Identification of puerarin and its metabolites in rats by liquid chromatography-tandem mass spectrometry

Puerarin (daidzein-8-C-glucoside) is the major bioactive isoflavone of kudzu root (the root of Pueraria lobata). Its metabolic fate, however, is not well-known. In this study, a sensitive and specific LC-ESI-MS/MS method for the determination of puerarin and its metabolites daidzein, dihydrodaidzein, and equol was developed for their analysis in biological samples. Two new metabolites of puerarin, mono- and dihydroxylated derivatives, were detected in the urine and feces of rats after oral administration. The persistence of puerarin in blood and urine as the principal metabolic form for the period of 4-72 h after oral administration suggested that puerarin is rapidly absorbed from the intestine without metabolism. Its presence in organs such as the brain suggests that this glucoside may enter tissues by specific transport pathways. Study of these metabolites may provide further understanding of the health beneficial effects of puerarin in kudzu dietary supplements.     

Method for analysis of tannic acid and its metabolites in biological samples: application to tannic acid metabolism in the rat

A new analytical method for measuring tannic acid (TA) using tannase was developed and applied to the investigation of TA metabolism in the rat following oral administration at a dose of 1.0 g/kg. The proposed method for TA determination was based on the enzymatic hydrolysis of TA to gallic acid (GA) and subsequent determination by HPLC. TA metabolites were determined by HPLC. 4-O-Methylgallic acid (4-OMGA), pyrogallol (PY), and resorcinol (RE) were detected in serum. TA was excreted into urine as GA (0.01%), 4-OMGA (0.10%), PY (0.24%), and RE (2.06%) and into feces as TA (62.74%), GA (0.19%), PY (0.02%), and RE (0.76%) within 54 h after oral administration. It was suggested that >60% of TA remained unchanged but that some was hydrolyzed to GA by tannase in the intestine and further metabolized to 4-OMGA, PY, and RE.     

Metabolism of grape seed polyphenol in the rat

The metabolism of grape seed polyphenol (GSP) has been investigated in rats by high-performance liquid chromatography analysis of the serum and urinary concentrations of the GSP metabolites (+)-catechin (CT), (-)-epicatechin (EC), 3'-O-methyl-(+)-catechin, and 3'-O-methyl-(-)-epicatechin. The serum concentration of these four metabolites reached a maximum 3 h after the oral administration of GSP. The urinary excretion of these GSP metabolites accounted for 0.254% (w/w) of the administered dose of GSP (1.0 g/kg), and the majority of these metabolites were excreted within 25 h of oral administration. The serum concentration and urinary excretion of these metabolites were also compared after the oral administration of different GSP monomers (gallic acid, CT, and EC), normal GSP, and the high molecular weight components of GSP (GSPH). No metabolites were detected in the serum of rats given GSPH. The urinary percentage excretion of the GSP metabolites derived from the respective monomers (CT or EC) did not vary with the administration of different substances (CT or EC, GSP, or GSPH). Taken together, these results suggest that only the monomers of GSP are absorbed and metabolized.     

Liquid chromatographic multicomponent method for determination of residues of ipronidazole, ronidazole, and dimetridazole and some relevant metabolites in eggs, plasma, and feces and its use in depletion studies in laying hens

A simple, rapid liquid chromatographic (LC) method that uses UV/VIS detection has been developed for the determination in eggs of residues of the histomonostats dimetridazole (DMZ), ronidazole (RON), ipronidazole (IPR), and side-chain hydroxylated metabolites of DMZ and RON. Sample pretreatment includes an aqueous extraction, purification with an Extrelut cartridge, and acid partitioning with isooctane. An aliquot of the final aqueous extract is injected into a reverse-phase LC system; detection is performed at 313 nm. The limits of determination are in the 5-10 microgram/kg range. A UV/VIS spectrum can be obtained at the 10 microgram/kg level by using diode-array UV/VIS detection. Recoveries are between 80 and 98% with a coefficient of variation of about 5%. Some 20 samples can be analyzed per day. A side-chain hydroxylated metabolite of IPR can also be detected with this method, as demonstrated with samples from animal experiments. After a single oral dose of the drugs to laying hens, residues of the parent compound and/or the hydroxylated metabolites could be detected in eggs 5-8 days after dosing. Plasma distribution and excretion in feces were established both with and without deconjugation. DMZ and IPR were extensively metabolized to hydroxylated nitroimidazole metabolites; RON was excreted mainly as the parent compound.     

Identification of rat urinary and fecal metabolites of a new herbicide, pyribenzoxim

Rats were treated with pyribenzoxim (O-[2,6-bis[(4,6-dimethoxy-2-pyrimidinyl)oxy]benzoyl]oxime), a new herbicide, to investigate the related metabolites in urine and feces. Metabolites were identified using LC/MS (electrospray ionization) and GC/MS (electron impact ionization) following the relatively simple and rapid extraction and purification procedures. Three metabolites were identified in urine either from oral gavage or intravenous (iv) injection. They were benzophenone oxime (BO), benzophenone oxime glucuronide (BOG), and 2-hydroxy-6-(4,6-dimethoxypyrimidin-2-yloxy)benzoic acid (HDB). Benzophenone oxime was present in larger quantity than BOG and HDB in urine from oral treatment, while the case was opposite in urine from iv treatment. Glucuronide conjugate was confirmed unambiguously by enzyme hydrolysis. 2,6-Bis(4,6-dimethoxypyrimidin-2-yloxy)benzoic acid (KIH-2023) and benzophenone were identified in feces. Benzophenone was confirmed by GC/MS and HPLC/DAD since LC/MS could not produce an ESI spectrum. On the basis of the results obtained, a metabolic map of pyribenzoxim is proposed.