[The Configuration of Tadalafil and Tadalafil Analogues Found in Dietary Supplements].

This study determined the configuration of the isomers of tadalafil, nortadalafil, and homotadalafil in dietary supplements. The products purchased over the Internet studied included a honey product and a tablet, which contained tadalafil, and a candy, which contained nortadalafil and homotadalafil. Each of the pharmaceutical ingredients isolated from the products was measured with circular dichroism (CD).As a result, the CD spectrum of each isolated pharmaceutical ingredient was found to align with the standard CD spectrum of the 6R,12aR isomer, confirmed that each isolated tadalafil or tadalafil analogue included in a 6R,12aR isomer. According to a report, among the stereoisomers of tadalafil, the 6R,12aR isomers have the most potent inhibitory activities of phosphodiesterase-type-5. From the report, the potential strength of the inhibitory activity of the 6R,12aR isomers of nortadalafil and homotadalafil was suggested. Therefore, it seemed that the 6R,12aR isomer often used in the product.

Characterization of a new illicit phosphodiesterase-type-5 inhibitor identified in the softgel shell of a dietary supplement.

A new sildenafil analog has been identified in the softgel shell of a dietary supplement. The compound was investigated by UV spectroscopy and high-resolution MS analysis, leading to the proposed structure 1-methyl-5-{5-[2-(4-methylpiperazin-1-yl)acetyl]-2-propoxyphenyl}-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one. A synthetic reference compound with the proposed structure was prepared, and the two sets of analytical data were compared, confirming the structure of the new compound. The compound was named propoxyphenyl noracetildenafil from its structure and similarity with the known compound.

Enantioseparation of the carboxamide-type synthetic cannabinoids N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide and methyl [1-(5-fluoropentyl)-1H-indazole-3-carbonyl]-valinate in illicit herbal products.

Synthetic cannabinoids, recently used as alternatives to Cannabis sativa, are among the most frequently abused drugs. Identified in 2014, the synthetic cannabinoids N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide (5F-AB-PINACA) and methyl [1-(5-fluoropentyl)-1H-indazole-3-carbonyl]-valinate (5F-AMB) are carboxamides composed of 1-(5-fluoropentyl)-1H-indazole-3-carboxylic acid and valine amide/methyl ester. Because of their composition, these molecules have pairs of enantiomers derived from the chiral center of their amino acid structures. Previous studies on the identification of 5F-AB-PINACA and 5F-AMB did not consider the existence of enantiomers, and there have been no reports on the enantiopurities of synthetic cannabinoids. We synthesized both enantiomers of these compounds and then separated the enantiomers by liquid chromatography-high-resolution mass spectrometry using a column with a chiral stationary phase consisted with amylose tris (3-chloro-4-methylphenylcarbamate). Under the optimized conditions, the enantiomer resolutions were 2.2 and 2.3 for 5F-AB-PINACA and 5F-AMB, respectively. Analysis of 10 herbal samples containing 5F-AB-PINACA and one herbal sample containing 5F-AMB showed that they all contained the (S)-enantiomer, but the (R)-enantiomer was only detected in two samples and at a ratio of less than 20%.

Simultaneous identification of 18 illegal adulterants in dietary supplements by using high-performance liquid chromatography-mass spectrometry.

We developed a method for the identification of 18 illegal adulterants in dietary supplements for erectile dysfunction by using high-performance liquid chromatography-mass spectrometry. The separation was achieved on a Cosmosil 3C18-EB column. The mobile phase consisted of 0.1% formic acid solution and 0.1% formic acid in acetonitrile, with gradient elution at a flow rate of 0.15 mL/min. The proposed method may be useful for the identification of illegal adulterants and for quality control of dietary supplements.

Simultaneous identification of hydroxythiohomosildenafil, aminotadalafil, thiosildenafil, dimethylsildenafil, and thiodimethylsildenafil in dietary supplements using high-performance liquid chromatography-mass spectrometry.

We developed a method for the separation and identification of illegal adulterants (hydroxythiohomosildenafil, aminotadalafil, thiosildenafil, dimethylsildenafil, and thiodimethylsildenafil) from dietary supplements using high-performance liquid chromatography-mass spectrometry. The separation was achieved on a C18 column: the mobile phase consisted of 5 mM ammonium formate (pH 6.3)-acetonitrile (75 : 25, v/v) and acetonitrile, with gradient elution at a flow rate of 0.2 mL/min. The proposed method could also be used to separate vardenafil, homosildenafil, and dimethylsildenafil, all of which have the same molecular weight. Furthermore, the proposed method could simultaneously separate hydroxythiohomosildenafil, aminotadalafil, thiosildenafil, dimethylsildenafil, thiodimethylsildenafil, vardenafil, and homosildenafil. Thus, this method may be useful to identify medicinal ingredients for erectile dysfunction and their analogs and to control the quality of dietary supplements.

A simple and selective detection method for aristolochic acid in crude drugs using solid-phase extraction.

The official Japanese method for analyzing aristolochic acid I (AA-I) in Asiasarum root using conventional high-performance liquid chromatography (HPLC) is described in the Japanese Pharmacopoeia, Sixteenth Edition. Interfering peaks of AA-I sometimes appear after HPLC analysis of crude drugs. A selective analytical method is needed to determine definitively whether AA-I is present in crude drugs. In this study, we developed a selective method that combined solid-phase extraction and liquid chromatography/mass spectrometry (LC/MS) which may be useful for identifying AA-I in crude drugs and for quality control.