Tohru Kishi

The use of a highly sulfated cyclodextrin for the simultaneous chiral separation of amphetamine-type stimulants by capillary electrophoresis.

We investigated the simultaneous chiral separation of nine amphetamine type stimulants (dl‐norephedrine, dl‐norpseudoephedrine, dl‐ephedrine, dl‐pseudoephedrine, dl‐amphetamine, dl‐methamphetamine, dl‐methylenedioxyamphetamine (MDA), dl‐methylenedioxymethamphetamine (MDMA), and dl‐methylenedioxyethylamphetamine (MDEA)) by capillary electrophoresis using highly sulfated γ‐cyclodextrin (SU(XIII)‐γ‐CD) as a chiral selector. Three different approaches using SU(XIII)‐γ‐CD with 50 mM phosphate background electrolyte were designed; (I) high CD concentration (10 mM SU(XIII)‐γ‐CD) at neutral pH (pH 7.0) in the normal polarity mode, (II) low CD concentration (1.0 mM) at low pH (pH 2.6) in the normal polarity mode and (III) high CD concentration at low pH (pH 2.6) in the reversed‐polarity mode. In mode (II), the effects of adding three neutral CDs (β‐CD, dimethyl‐β‐CD and hydroxypropyl‐β‐CD) were also investigated. The best separation was obtained after optimizing mode (III) as follows: run buffer of 10 mM SU(XIII)‐γ‐CD with 50 mM phosphate background electrolyte at pH 2.6, applied voltage of –12 kV and capillary temperature of 15°C.

Methamphetamine impurity profiling using a 0.32 mm i.d. nonpolar capillary column

Classification of seized methamphetamine by impurity profiling can provide very useful information in criminal investigations of drug traffic routes, sources of supply and relationships between seizures. The aim of this study is to improve and develop an analytical method for detecting impurities such as starting materials and by-products in illegally prepared methamphetamine.HCl samples. A 50mg sample of methamphetamine.HCl was dissolved in 1 ml of buffer solution (four parts 0.1M phosphate buffer pH 7.0 and one part 10% Na2CO3). Impurities were extracted with 0.5 ml of ethyl acetate containing four internal standards (ISs) (n-decane, n-pentadecane, n-nonadecane and n-hexacosane) and analyzed by gas chromatography (GC) using a flame ionization detector (FID) on a DB-5 capillary column (0.32 mmi.d. x 30 m, film thickness 1.0 microm). The use of a middle-bore column offered better separation of the impurity peaks. The correction of the retention times of impurity peaks with four ISs made peak identification very accurate for subsequent data processing. Twenty-four characteristic peaks were selected for comparison and similarity and/or dissimilarity between samples, and the data were evaluated by the Euclidean distance of the relative peak areas after logarithmic transformation. The results indicate that the present method would be useful for methamphetamine impurity profiling.

Isolation, identification and excretion profile of the principal urinary metabolite of the recently banned designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP) in rats.

The metabolism of 1-(3-trifluoromethylphenyl)piperazine (TFMPP), a recently banned designer drug, in rats was studied by analysing its urinary metabolites. p-Hydroxy-TFMPP (p-OH-TFMPP) was isolated and identified as the main metabolite by using nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry and high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS). The time-course excretion profiles of TFMPP and p-OH-TFMPP in rats were investigated following a single intraperitoneal dosing of 5 mg kg−1 TFMPP by using an optimized analytical procedure that combined solid-phase extraction and LC-ESI MS techniques. The cumulative amount of p-OH-TFMPP excreted within the first 48 h reached approximately 64% of the dose, of which 70% was the glucuronide conjugated form. The cumulative amount of parent TFMPP excreted was less than 0.7% of the dose. The results suggest that p-OH-TFMPP would be the most relevant metabolite to be detected for TFMPP exposure in the forensic and clinical analysis of human urine.

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.

In vivo metabolism of 2,5-dimethoxy-4-propylthiophenethylamine in rat

The in vivo metabolism of 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), a ring-substituted psychoactive phenethylamine, was studied in rat. Male Wistar rats were administered 10 mg/kg 2C-T-7 hydrochloride orally, and 24-h urine fractions were collected. After enzymatic hydrolysis of the urine sample, the metabolites were extracted by liquid–liquid extraction and analyzed by liquid chromatography/mass spectrometry. 2C-T-7-sulfoxide, N-acetyl-2C-T-7-sulfoxide, N-acetyl-2,5-dimethoxy-4-methylthiophenethylamine-sulfoxide, N-acetyl-2,5-dimethoxy-4-(2-hydroxypropylthio)phenethylamine-sulfoxide, and N-acetyl-2,5-dimethoxy-4-(2-hydroxypropylthio)phenethylamine-sulfone were detected as the primary metabolites of 2C-T-7. These findings suggest that sulfoxidation, sulfone formation, hydroxylation of the propyl side chain at the β-position, and S-depropylation followed by methylation of thiol were the major metabolic pathways of 2C-T-7 in rat.

Quantitative optical study of I2-doped polyacetylene

Abstract The relation between dopant concentration and adsorption spectra of iodine-doped polyacetylene films is studied quantitatively with films whose iodine contents are analysed by radioactivation analysis. It is shown that the dopant content of thin polyacetylene film can be estimated from the absorption spectra. For heavily iodine-doped film, optical constants are determined from measured infrared, visible and ultraviolet spectra by the aid of the Kramers–Kronig relation. The absorption coefficient of 64% iodine-doped film at the absorption maximum of the mid-gap band, 7500 cm −1 , is 2.5 × 10 5 cm −1 and that of the same film at the adsorption maximum of the pentaiodide ion, 19 000 cm −1 , is 2.9 × 10 5 cm −1 , whereas the maximum value for undoped film at 18 500 cm −1 is 1.5 × 10 5 cm −1 ( cis -rich form).

A Fatal Case of Suspected Anaphylaxis with Cefoperazone and Sulbactam: LC-MS Analysis

Cefoperazone and sublactam are prescribed in combination and used in the treatment of moderate to severe bacterial infections. Serious anaphylaxis is a rare side effect. This report describes a fatal case of suspected anaphylaxis after intravenous administration of a combination of the two drugs. Heart blood was analyzed for cefoperazone by protein precipitation with acetonitrile and by liquid‐liquid precipitation for sublactam after protein precipitation with aqueous acetonitrile, followed by tandem mass spectrometry in the product ion scan mode for identification and by liquid chromatography mass spectrometry in the selected ion monitoring mode for quantitation. Calibration curves for cefoperazone and sublactam were linear over the range 0.07 to 1.93 and 0.046 to 0.914 μg/ml respectively. The decedents blood concentrations of cefoperazone and sublactam were 0.368 and 0.143 μg/ml respectively. As these concentrations were below concentrations reported after single dosing studies and below those considered to be minimally inhibitory, death was presumed to have been caused by hypersensitivity and not an overdose. In conclusion, this procedure is useful for detecting and quantitating cefoperazone and sublactam in postmortem blood and may be useful in the evaluation of anaphylaxis.

Application of terahertz spectroscopy to abused drug analysis

In the field of forensic chemistry, the identification of abused drugs is of great importance. In this study, we applied terahertz spectroscopy for identifying various types of abused drugs. Most of these drugs showed characteristic terahertz absorption spectra in the range of 20-100 cm/sup -1/ (0.6-3 THz), which is sufficient to differentiate them from one another.

The metabolism of 1-phenyl-2-(N-methyl-N-furfurylamino)propane (furfenorex) in the rat in vivo and in vitro

The metabolism of 1-phenyl-2-(N-methyl-N-furfurylamino)propane (furfenorex) was studied in the rat in vivo and in vitro. Nine metabolites with only traces of the unchanged drug were obtained from urine after oral administration of furfenorex to rats. The major metabolite was an acidic compound, isolated and identified as 1-phenyl-2-(N-methyl-N-gamma-valerolactonylamino)propane. Amphetamine, methamphetamine and their hydroxylated metabolites were excreted as minor metabolites. Metabolites excreted in two days after administration of the drug amounted to about 20% of dose. The acidic metabolite, a major metabolite in vivo, was not detected after incubation of furfenorex with rat-liver microsomes. The major metabolic routes of furfenorex in vitro were N-demethylation and N-defurfurylation which produced 1-phenyl-2-(N-furfurylamino)propane (furfurylamphetamine) and methamphetamine, respectively. The formation of furfurylamphetamine and methamphetamine were catalysed by rat-liver microsomes supplemented with NADPH and O2, and were inhibited by either SKF 525-A or CO. The formation of both metabolites were inhibited by 2-methyl-1,2-bis-(3-pyridyl)-1-propanone (metyrapone), but not by 7,8-benzoflavone. They were enhanced by pretreatment of rats with phenobarbitone, but not with 3-methylcholanthrene. These data suggested that N-demethylation and N-defurfurylation of furfenorex were mainly mediated by cytochrome P-450 but not cytochrome P-448.

Spectral Studies on the Charged Soliton of Polyacetylene

Abstract The optical spectra of polyacetylene doped with iodine (p type) or sodium (n type) are investigated in the infrared and visible region. The change of spectra with doping is measured quantitatively. Model structures of the charged soliton lattice are suggested for p and n type chains of the highest doping levels. The reflection spectra of (CHIy)x and (CDIy)x for heavy doped films are measured and analyzed by five transitions existing in 0 - 24000 cm−1 region. By lowering the temperature to 30 K, the gapless transition is disappeared presumably because the lattice with the charged soliton is frozen.