Determination of a new type of phosphodiesterase-5 inhibitor, thioquinapiperifil, in a dietary supplement promoted for sexual enhancement.

A new type of phosphodiesterase-5 (PDE-5) inhibitor, thioquinapiperifil (1), was found in dietary supplements. LC-MS analysis indicated that the supplements contain two major compounds. One was identified as thiodenafil (synonym: thiosildenafil) by direct comparison with the authentic compound. The other showed a molecular weight of 448, and accurate mass measurement showed its elemental composition to be C(24)H(28)N(6)O(1)S(1). Together, the mass and NMR spectrometric data revealed that the compound is an imidazoquinazoline derivative: 3-ethyl-1,3-dihydro-8-[[[2-[4-(hydroxymethyl)-1-piperidinyl]phenyl]methyl]amino]-2H-imidazo[4,5-g]quinazoline-2-thione. This compound had been synthesized as a PDE-5 inhibitor, formerly reported as KF31327 by Kyowa Hakko Kogyo Co., Ltd. Considering this compound's general properties, it has been renamed thioquinapiperifil with the agreement of Kyowa Hakko Kogyo Co., Ltd. The detection of imidazoquinazoline-type compounds in dietary supplements has not been reported. Quantitative analysis showed that the contents of 1 and thiodenafil in the products were about 13-15 mg/tablet (43-48 microg/mg) and about 0.4 mg/tablet (1 microg/mg), respectively.

[Analytical data of designated substances (Shitei-Yakubutsu) controlled by the Pharmaceutical Affairs Law in Japan, part I: GC-MS and LC-MS].

In the last 10 years, many analogs of narcotic substances have been widely distributed in Japan as easily available psychotropic substances and this has become a serious problem. They have been sold as video cleaners, incense and reagents via the Internet or in video shops. They are not controlled under the Narcotics and Psychotropics Control Law because their pharmacological effects have not yet been proved scientifically. As a countermeasure to prevent the abuse of these substances, the Ministry of Health, Labor and Welfare amended the Pharmaceutical Affairs Law in 2006 so that 31 non-controlled psychotropic substances (11 tryptamines, 11 phenethylamines, 6 alkyl nitrites, 2 piperazines and salvinorin A) and 1 plant (Salvia divinorum) are now controlled as "Designated Substances (Shitei-Yakubutsu)" as of April 2007. Five other compounds (4 phenethylamines and 1 piperazine) were also added to this category in January 2008. In this study, we developed simultaneous analytical methods for these designated substances using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) and present retention times, UV spectra, electron ionization (EI), GC-MS, and electrospray ionization (ESI) LC-MS data.

The disposition into hair of new designer drugs; methylone, MBDB and methcathinone.

The disposition into hair of methylone and other new designer drugs, methcathinone and MBDB, was studied with the animal model. Moreover, the incorporation rates of these drugs were compared with those of their related eight compounds previously studied in order to evaluate their incorporation tendency into hair and the usefulness of hair specimens for the retrospective confirmation of the use of these drugs. When the ratio of hair concentration to AUC in plasma ([Hair]/AUC) was represented as an index of the incorporation rate of drugs into hair, the [Hair]/AUC of methylone was 14 times higher than that of methcathinone. It might support earlier findings that the methylenedioxy group on the benzene ring leads to considerably higher incorporation rates. However, [Hair]/AUC of methylone was five-sevenths times lower in comparison with that of MDMA. This suggested that the beta-carbonyl group leads to lower incorporation rates. Although methylone has both groups in its structure, the positive effect of the methylenedioxy group may be stronger than the negative effect of the beta-carbonyl group. On the other hand, the [Hair]/AUC of MBDB, which has methylenedioxyphenyl-2-butanamine structure, was higher than that of MDMA while that of methcathinone, having beta-ketone in its structure, was extremely low. In conclusion, as with MA and MDMA, the incorporation tendency of methylone and MBDB (except for methcathinone) into hair is relatively high, and a hair sample would be a good specimen for the confirmation of retrospective use of these drugs.