A method for screening for various sedative-hypnotics in serum by liquid chromatography/single quadrupole mass spectrometry

A screening method for the detection of sedative-hypnotics in serum is described. The target drugs, which include practically all the sedative-hypnotics distributed in Japan, consisted of 5 barbiturates, 30 benzodiazepine-related drugs and 11 other sedative-hypnotics (i.e., apronalide, bromisovalum, chloral hydrate, triclofos, chlorpromazine, promethazine, diphenhydramine, hydroxyzine, zopiclone, zolpidem and tandospirone). Thirty-nine analytes, selected in terms of the pharmacokinetics of the target drugs, in human serum were screened using a combination of mixed-mode solid-phase extraction and liquid chromatography/electrospray-ionization single-quadrupole mass spectrometry. The detection limits (non-basic analytes, 1-50 ng/ml; basic analytes, 0.1-5 ng/ml) were sufficient to permit the screening of a single therapeutic administration of a target drug.     

Analysis of wrapped or cased object by a hand-held X-ray fluorescence spectrometer

Metals, alloys, and poisoned food were analyzed with a hand-held X-ray fluorescence (XRF) spectrometer, with a shield (wrapping or casing material) inserted between these objects and the spectrometer, in order to examine the possibility of analyzing the contents of packages. Elements such as Fe, Cr, Ni, Cu, Zn, Pb, Mo, and As were detected in the objects. The fluorescent intensity of each element in the object decreased exponentially as the thickness of the shield increased, and the degree of decrease depended on both the material of the shield and the energy of fluorescent X-rays. The thickness of the shield can be calculated by using the intensity ratio Fe Kbeta/Kalpha or Pb Lbeta/Lalpha when the object is iron or lead, or by using the intensity of the Compton scattering of incident X-rays. The original peak intensity, i.e. intensity without a shield, of an element in an object can be estimated with the thickness of the shield obtained. Because the original peak intensity is calculated using an exponential function of the thickness of the shield, calculation of the intensity ratio, e.g. Zn Kalpha/Cu Kalpha for brass, is effective for cancelling the estimation error for the thickness of the shield. The composition of brass and steel can be estimated with an error of less than 30% by using the intensity of the Compton scattering.     

Australia's Response to the Indochina Crisis of 1954 amidst the Anglo‐American Confrontation

Meeting in Berlin in February 1954, the Great Powers decided to convene an international conference in Geneva in April to discuss the restoration of peace in Indochina and thereby opened the door to a crisis. Their decision triggered a Vietnamese communist offensive against the French union forces at Dien Bien Phu, and a subsequent US proposal for multilateral military intervention which put great strain upon Anglo‐American relations. This article examines Australia's response to the Indochina crisis of 1954 amidst the Anglo‐American confrontation, focusing on the disagreement between the UK and USA with its origins in their different assessments of the will of the French and Vietnamese to continue fighting; on the impetus that events such as the Berlin conference gave to Australia to redefine its own position on Indochina; and on the (relatively minor) role which Australia, as the military situation in Indochina worsened, played in assisting the US to alter its proposal for allied military intervention.     

Synthesis and Analysis of Glucuronic Acid‐Conjugated Metabolites of 4‐Bromo‐2,5‐Dimethoxyphenethylamine

In the study reported here, two glucuronic acid‐conjugated metabolites of 4‐bromo‐2,5‐dimethoxyphenethylamine (2C‐B)—a ring‐substituted psychoactive phenethylamine—were chemically synthesized for the first time and a method for analyzing them in urine was developed. β‐D‐Glucuronide of 4‐bromo‐2,5‐dimethoxyphenylethylalcohol was successfully synthesized using methyl 2,3,4‐tri‐Ο‐acetyl‐1‐O‐(trichloroacetimidoyl)‐α‐D‐glucuronate as a glucuronyl donor and boron trifluoride diethylether complex as a Lewis acid catalyst. β‐D‐Glucuronide of 4‐bromo‐2,5‐dimethoxyphenylacetic acid was synthesized by condensing 4‐bromo‐2,5‐dimethoxyphenylacetic acid and benzyl D‐glucuronate followed by benzyl group deprotection based on catalytic hydrogenation. Two glucuronic acid‐conjugated metabolites of 2C‐B in urine were qualitatively and semiquantitatively evaluated via direct liquid chromatography/mass spectrometry (LC/MS) analysis of a diluted urine sample. The simple method proposed is expected to be useful for studying the metabolic fate of 2C‐B.     

Determination of salvinorin A and salvinorin B in Salvia divinorum-related products circulated in Japan

Two major salvinorins, salvinorin A (SalA) and salvinorin B (SalB), in three Salvia divinorum dried leaf products and nine of its "concentrated extract" products circulated in Japan were determined. These ingredients were extracted twice with acetonitrile and decolored with graphite carbon powder. SalA and SalB were confirmed by liquid chromatography-tandem mass spectrometry in product ion scan mode, and quantified by high-performance liquid chromatography with UV detection (for SalA) and by mass spectrometry in single ion monitoring mode (for SalB). The SalA/SalB contents (mug/mg) were in the range of 3.2-5.0/0.10-0.17 in the dried leaf products and 4.1-38.9/0.26-2.42 in the "concentrated extract" products. These findings would be useful for analysis of S. divinorum-related products circulated in the drug market.     

Comparison and classification of methamphetamine seized in Japan and Thailand using gas chromatography with liquid-liquid extraction and solid-phase microextraction

Methamphetamine (MA) is one of the most frequently abused drugs worldwide. The aim of this study is to improve the analytical method for profiling MA impurity in order to compare and classify MA crystals seized in different countries and to investigate the relationships between seizures. To compare MA samples seized in Japan and Thailand, the following analytical method was adopted. A 50mg sample of MA.HCl was dissolved in 1ml of buffer solution (four parts 0.1M phosphate buffer, pH 7.0, and one part 10% Na(2)CO(3)), impurities were extracted with 0.5ml of ethyl acetate containing four internal standards (n-decane, n-pentadecane, n-eicosane and n-octacosane) and analyzed by gas chromatography with a flame ionization detector on a DB-5 capillary column (0.32mm i.d.x30m, film thickness 1.0mum). Fourteen characteristic peaks on chromatograms were selected for the comparison and classification of samples, and the data were evaluated by the Euclidean distance of the relative peak areas after logarithmic transformation. Sixty-nine samples seized in Japan and 42 seized in Thailand were analyzed. The samples were classified into four groups roughly by cluster analysis. In addition, when it was difficult to compare samples that had fewer impurities on chromatograms obtained from liquid-liquid extraction (LLE), solid-phase microextraction (SPME) was effective. Because many characteristic peaks were detected using SPME, SPME made it easy to compare samples of high purity. The combination of LLE and SPME was useful for impurity profiling of MA samples seized in different countries.     

Interaction of 3,4-methylenedioxymethamphetamine and methamphetamine during metabolism by in vitro human metabolic enzymes and in rats

Illicit amphetamine-type stimulant (ATS) tablets commonly contain one or more active ingredients, which have hallucinogenic and/or stimulant effects. Because components such as 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MA) in ATS tablets have similar chemical structures, they could be metabolized by common metabolic enzymes. To investigate potential metabolic interactions of ATS tablet components, we studied the in vitro metabolism of MDMA and MA using human metabolic enzymes. MDMA and MA were mainly metabolized by cytochrome P450 2D6 (CYP2D6) and mutually inhibited the production of their main metabolites. In vivo experiments were also performed using intravenous administration of MDMA, MA, or their mixture to rats. The plasma concentrations of MDMA and MA after co-administration were higher than those after administration of MDMA or MA alone. The results in this study imply that multiple components in ATS tablets can interact to mutually inhibit their metabolism and potentially enhance the toxicity of each component.     

Dulles’s second visit to Japan: The Tokyo talks of 1951

In January–February 1951, intensive negotiations were conducted in Tokyo between the Japanese and American governments about Japan’s roles in American strategy in Asia. The United States expected Japan to play two vital roles in the cold war. The first was that Japan could act as a potential offensive base from which to mount warfare against Soviet Russia and communist. China. the second was that Japan would serve as a supplementary balancer in the maintenance of the balance of power in Northeast Asia through the reactivation of her defense forces. This article, examining the Japanese government’s preparations for the Tokyo talks, discusses Japanese-American negotiations on a bilateral base arrangement and rearmament. It is argued that, although the United States succeeded in securing Japan as a major strategic base in the cold war by obtaining Japanese agreement to the U.S. proposal for stationing requirements for post-treaty American bases and troops, it failed in having Japan accept a U.S. plan for the revitalization of Japanese power because of the Japanese government’s reservation about rearmament.