Structure elucidation of sildenafil analogues in herbal products

Blok-Tip, Leonore; Zomer, Bert; Bakker, Frank; Hartog, K.D; Hamzink, M.; Hove, Jan ten; Vredenbregt, M.J.; Kaste, D. de

doi:10.1080/02652030412331272467

Cited by 103 publications

(59 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus far, a large number of analogues of sildenafil, tadarafil and vardenafil have been reported, [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] while a new type of phosphodiesterase-5 (PDE-5) inhibitor, (R)-xanthoanthrafil, an anthranilic acid derivative, has been found in a dietary supplement advertising sexual enhancement for men. 24) (R)-Xanthoanthrafil was first synthesized as a candidate compound for the treatment of ED by Fujisawa Pharmaceutical Co., Ltd. (currently Astellas Pharma Inc., Tokyo, Japan), 25) and was reported as a PDE-5 inhibitor, FR226807, after the manufacturer discontinued the process of developing the drug for approval.…”

mentioning

confidence: 99%

Isolation and Structural Elucidation of Cyclopentynafil and N-Octylnortadalafil Found in a Dietary Supplement

Hasegawa

Takahashi

Saijo

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

A new sildenafil analogue, cyclopentynafil (1) and a new tadalafil analogue, N-octylnortadalafil (2) were isolated from a dietary supplement illegally marketed for erectile dysfunction. The structures of the sildenafil and tadalafil analogues were elucidated by using HPLC-photodiode array (PDA), LC-MS, high-resolution MS, NMR and circular dichroism (CD). These compounds were determined to be 5- In this paper, we report the analysis and structural elucidation of a new sildenafil analogue, cyclopentynafil and a new tadalafil analogue, N-octylnortadalafil, that were isolated from a dietary supplement illegally marketed for erectile dysfunction. ExperimentalChemicals and Reagents HPLC-grade acetonitrile and all other reagents (analytical grade) were purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan).Sample The examined product was purchased as a processed food composed mainly of walnuts through the Internet and was composed of four pieces of ivory tablets (400 mg). The product properties were as follows: product name; Highperwalnup 2, producing company; Art Creation Co., Ltd., sales company; Ogawa Planning Co., Ltd., date of purchase; December 28, 2007.Preparation of Sample Solution One tablet was finely powdered, and 100 mg of the powder was ultrasonically extracted in 10 ml of 70% methanol for 15 min. The extract was centrifuged at 1700ϫg. The supernatant was filtered through a 0.45 mm filter. The filtrate was used for HPLC, and a portion of it was diluted 10-fold with methanol for liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analysis.HPLC Analysis HPLC analysis was performed using a JASCO PU-2089 apparatus equipped with a photodiode array (PDA) detector model MD-2015 (JASCO Corporation, Tokyo, Japan). The sample solution was separated by using a TSK-GEL ODS-80Ts column (150ϫ4.6 mm i.d., 5 mm, Tosoh Co., Tokyo, Japan). The mobile phase was an acetonitrile/water/phosphoric acid (100 : 900 : 1) mixture solution containing 5 mmol/l sodium hexanesulfonate (eluent A) and an acetonitrile/water/phosphoric acid (900 : 100 : 1) mixture solution containing 5 mmol/l sodium hexanesulfonate (eluent B). The gradient elution was started at 90% eluent A, and was linearly decreased to 55% A in 25 min and to 10% A in 44-49 min. The flow rate of the mobile phase was set at 1.0 ml/min, and the injection volume was 20 ml. The column temperature was maintained at 40°C. The PDA detection wavelength was set from ultraviolet (UV) 200 to 400 nm, and max-plot chromatographic monitoring was performed (200-400 nm).LC-ESI-MS Analysis LC-ESI-MS analysis was performed using a Waters alliance 2695 separation module and ZQ mass spectrometer (Waters Corporation, Milford, MA, U.S.A.). The sample solution was separated by using an Atlantis dC18 column (150ϫ2.1 mm i.d., 3 mm, Waters Corporation). The mobile phase was 0.1% formic acid aqueous solution (eluent A) and acetonitrile containing 0.1% formic acid (eluent B). The gradient elution began at 95% eluent A, and linearly decreased to 80% A in 15 min and ...

show abstract

mentioning

confidence: 99%

Isolation and Structural Elucidation of Cyclopentynafil and N-Octylnortadalafil Found in a Dietary Supplement

Hasegawa

Takahashi

Saijo

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…It is potentially dangerous for consumers to take adulterated dietary supplements. Moreover, not only prescription drugs but also their analogues such as N-nitroso-fenfluramine 5) , homosildenafil 6) , acetildenafil 7) , hydroxyhomosildenafil 7) and aminotadalafil 8) have been detected. We have already established a HPLC screening method for synthetic drugs in dietary supplements, such as tonic medicines, anorexic agents, hypoglycemic agents, and so on῍ 2 .…”

Section: Introductionmentioning

confidence: 99%

Structural Elucidation of a Tadalafil Analogue Found in a Dietary Supplement

Hasegawa¹,

Saijo²,

Ishii³

et al. 2008

J. Food Hyg. Soc. Jpn

View full text Add to dashboard Cite

A tadalafil analogue was detected in a dietary supplement marketed for tonic e#ect, along with hydroxyhomosildenafil and aminotadalafil. The tadalafil analogue was isolated by preparative thin layer chromatography (TLC) and its structure was elucidated using high-performance liquid chromatography (HPLC), liquid chromatography electrospray ionization-mass spectrometry (LC-ESI-MS), Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The compound was determined to be methyl-1-(1,3-benzodioxol-5-yl)-2-(chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido [3,4-b]indole-3-carboxylate. This is the first report of detection of this compound in a dietary supplement.

show abstract

“…Structural analogs that have a partly modified structure of pharmaceuticals have been detected in some cases. [1][2][3] Although such analogs are considered to possess the same activities as their original compounds, little is known about their actual * To whom correspondence should be addressed: Department of Drug and Food Science, Shizuoka Institute of Environment and Hygiene, 4-27-2 Kita-ando, Aoi-ku, Shizuoka, Shizuoka, 420-8637, Japan. Tel.…”

Section: Introductionmentioning

confidence: 99%

Identification of Aminotadalafil and its Stereoisomers Contained in Health Foods Using Chiral Liquid Chromatography-Mass Spectrometry

Kurita

Mizuno

Kuromi

et al. 2008

JOURNAL OF HEALTH SCIENCE

View full text Add to dashboard Cite

Using chiral liquid chromatography-mass spectrometry (LC/MS), a simple and rapid identification test was developed for aminotadalafil [(6R,12aR)-2-amino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino[1 ,2 : 1,6]pyrido [3,4-b]indole-1,4-dione; RR-ATDF] and its stereoisomers contained in health foods, e.g. herbal products. A sample solution was prepared using methanol extraction. Analysis was performed on a chiral column with the mixture of 0.1% formic acid/acetonitrile (7 : 3) as mobile phase at 30• C. Each resolution value of four stereoisomers of ATDF was greater than 1.3. A mass spectrometer was used as a detector to enhance specificity by excluding the effects of general components derived from the sample. The four individual stereoisomers of ATDF in the health foods were identified based on their respective retention times. Results showed that structural conversions of RR-ATDF into (6R,12aS)-2-amino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino[1 ,2 : 1,6]pyrido [3,4-b]indole-1,4-dione (RS-ATDF) and (6S ,12aS)-2-amino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino[1 ,2 : 1,6]pyrido [3,4-b]indole-1,4-dione (SS-ATDF) into (6S ,12aR)-2-amino-6-(1,3-benzodioxol-5-yl)-2, 3,6,7,12,12a-hexahydropyrazino[1 ,2 : 1,6]pyrido [3,4-b]indole-1,4-dione (SR-ATDF) occurred under strongly basic conditions, which indicates that such conditions must be avoided during sample preparation. Using this method, RR-ATDF and SR-ATDF were detected in a health food; this is the first report describing that ATDF diastereomers are present in health foods.

show abstract

Structure elucidation of sildenafil analogues in herbal products

Cited by 103 publications

References 3 publications

Isolation and Structural Elucidation of Cyclopentynafil and N-Octylnortadalafil Found in a Dietary Supplement

Isolation and Structural Elucidation of Cyclopentynafil and N-Octylnortadalafil Found in a Dietary Supplement

Structural Elucidation of a Tadalafil Analogue Found in a Dietary Supplement

Identification of Aminotadalafil and its Stereoisomers Contained in Health Foods Using Chiral Liquid Chromatography-Mass Spectrometry

Contact Info

Product

Resources

About