Tetsukichi Niwaguchi

Determination of methamphetamine in hair after single and repeated administration to rat

Methamphetamine in hair after p.o. administration to rat was identified and determined by mass fragmentography (MF). Rat hair was washed with HCl/methanol, methanol and water. The hair was crushed in 0.6 M HCl, suspension was alkalized with Na2CO3, and extracted with chloroform/isopropanol. The extract obtained was purified by column chromatography on aluminium oxide. Concentrated eluate was trifluoroacetylated, and methamphetamine was identified and determined by MF. More than 20 pg of methamphetamine was detectable and less than 1 ng of that was determined by MF.Methamphetamine in hair collected from rat after p.o. administration of 20 mg/kg of the drug was detected and determined up to 8 days after. From hair of rat after 5-days or 14-days repeated administration of 20 mg/kg/day, methamphetamine was detected 25 or 45 days after the last administration, respectively.

The metabolism of 1-phenyl-2-(N-methyl-N-benzylamino)propane (benzphetamine) in vivo in the rat

1. The metabolism of 1-phenyl-2-(N-methyl-N-benzylamino)propane (benzphetamine) was studied in vivo in the rat. 2. Nine metabolites were obtained from urine after oral administration of benzphetamine to rats. The major metabolite, identified as 1-(p-hydroxyphenyl)-2-(N-benzylamino)propane, was formed by aromatic hydroxylation and N-demethylation. One of the minor metabolites was methamphetamine, formed by N-debenzylation. 3. Metabolites excreted in three days after administration of the drug amounted to about 40% of the dose.

Determination of d -methamphetamine in Urine after Administration of d - or dl -methamphetamine to Rats by Radioimmunoassay Using Optically Sensitive Antiserum

A radioimmunoassay was developed for the determination of d-methamphetamine in urine. Antiserum to d-methamphetamine was prepared in rabbits by immunization with d-N-4-aminobutylmethamphetamine conjugated with bovine serum albumin. d-1-[3H]-Methamphetamine was used as a labeled compound for radioimmunoassay. The specificity of the antibody against d-methamphetamine was determined by cross-reaction studies with optical isomers of methamphetamine and its analogs. The antibody was specific for d-methamphetamine and exhibited no significant cross-reaction with the l-isomers. This stereoselective assay was applied to determination of d-methamphetamine excreted in urine after oral administration of d- or dl-methamphetamine to rats.

Studies on Quantitative in situ fluorometry of lysergic acid diethylamide (lsd) on thin-layer chromatograms

Abstract The quantitative in situ fluorometry of LSD on thin-layer chromatograms was investigated. Reproducibilities for the range 0.1–2.0 μg of LSD on the same and different chromatograms were examined in both direct and internal standard methods The linear relationship between fluorescence emission intensity and amount of LSD was found in both methods. This technique has been applied to the determination of unchanged LSD in the photodecomposition process. It was noted that LSD was easily decomposed by ultraviolet irradiation.

Distribution and excretion of methamphetamine and its metabolites in rats. II: Time course of concentration in blood and distribution after multiple oral administration

The time-course of total blood radioactivity after oral administration of 3H-methamphetamine, following multiple oral administration of non-radioactive methamphetamine for 7 and 14 days to rats, was examined to elucidate the effects of multiple administration on enterohepatic circulation. Whole-body autoradiographs of rats after oral administration of 14C-methamphetamine showed high levels of radioactivity in contents of stomach and small intestine, bladder urine, liver, and various glands. Distribution of methamphetamine and the major metabolite in tissues during multiple dosing was investigated; accumulation occurred in brain, liver, testis and fat. Multiple oral administration of methamphetamine to rats slightly induced enzyme activities of N-demethylation and aromatic hydroxylation of methamphetamine in rat-liver 9000 g supernatant.

Rapid screening method for methamphetamine in urine by colour reaction in a sep-pak C18 cartridge

A simple screening method for methamphetamine in urine by colour reaction was developed. Methamphetamine, which is quantitatively retained in a Sep-Pak C18 cartridge, is (after a clean-up procedure) coloured by Simons reagent (consisting of sodium nitroprusside solution, sodium carbonate solution and acetaldehyde gas). The detection limit was 0.5 microgram/ml using 5 ml of urine sample. The results of the screening method agreed with those of thin-layer chromatography and gas chromatography-mass spectrometry.

Determination of nitrazepam and its main metabolites in urine by thin-layer chromatography and direct densitometry

A method for the direct quantitative densitometry of nitrazepam and its main metabolites (7-aminonitrazepam, 7-acetamidonitrazepam and 2-amino-5-nitrobenzophenone) in urine was developed. The unchanged drug and its metabolites were extracted with benzene-dichloromethane (4:1), subjected to thin-layer chromatography, and determined by direct ultraviolet densitometry. Recovery experiments showed that the method was quantitative. The limit of detection was 5 ng/ml for 2-amino-5-nitrobenzophenone and 10 ng/ml for other compounds. The method was applied to the determination of nitrazepam and its metabolites excreted in human urine after administration of 10 mg of the drug.

Multi-element determinations of trace elements in glass by instrumental photon activation analysis

Abstract An instrumental photon activation method is reported for multi-element determinations in glass. The concentrations of 17 elements in NBS standard glass can be determined by irradiation with 30-MeV bremsstrahlung and measurement of the resulting γ-rays with a Ge(Li) detector. The average of all relative standard deviations is 2.7%; the relative deviations from the NBS certified values range from 1.4 to 3.4%.

Actions of D-lysergic acid diethylamide (LSD) and its derivatives on 5-hydroxytryptamine receptors in the isolated uterine smooth muscle of the rat.

Several metabolites of D-lysergic acid diethylamide (LSD) such as D-lysergic acid ethyl, 2′-hydroxyethylamide (LEO), D-lysergic acid ethyl,vinylamide (LEV), D-lysergic acid ethylamide (LAE) and D-norlysergic acid diethylamide (norLSD) are formed by liver tissue and by Streptomyces. These metabolites and synthetic N6-alkyl substituted derivatives such as N6-ethyl-, N6-propyl, N6-allyl and N6-hexyl-D-norLDS (ethyl-, propyl-, allyl- and hexyl-norLSD, respectively) were studied for their anti-d-hydroxytryptamine (anti-5-HT) and oxytoxic activities on isolated rat uteri. The LSD derivatives had less anti-5-HT activity than LSD. Except for hexyl-norLSD, N6-alkyl substituted derivatives of LSD had higher oxytocic activities than LSD, LEO or LAE. Minimum effective concentrations as well as ED50 values for oxytocic activities of ethyl-norLSD, propyl-norLSD and allyl-norLSD were lower than that of LSD whereas those of the metabolites (LEO, LAE and norLSD) were higher than that of LSD. The oxytocic activity of allyl-norLSD was effectively antagonized by LSD and cyproheptadine, suggesting that this activity was due to its 5-HT-like action. These results suggest that N6-alkyl substituted derivatives (ethyl-, propyl-, allyl-norLSD) have higher, but the metabolites of LSD have lower affinity for 5-HT receptors than LSD, and that N6-substituted derivatives except for hexyl-norLSD have higher intrinsic activity than LSD.

Distribution and excretion of methamphetamine and its metabolites in rats III. Time-course of concentrations in blood and bile, and distribution after intravenous administration

The time-course of blood total radioactivity after i.v. administration of 3H-methamphetamine to rats showed a biphasic curve. The biological half-life of the alpha phase (t alpha 1/2) was 6.8 +/- 2.0 min, and that of the beta phase (t beta 1/2) was 11.3 +/- 0.8 h. The major metabolite in the blood was unconjugated p-hydroxymethamphetamine. The total radioactivity in bile peaked at 1.5 h after i.v. administration. The major metabolite in the bile was p-hydroxymethamphetamine glucuronide. The major compound excreted in urine was unchanged methamphetamine. Whole-body autoradiography was performed using 14C-methamphetamine, and tissue 3H concn. was determined after i.v. administration of 3H-methamphetamine to rats.