Analysis of undeclared synthetic phosphodiesterase-5 inhibitors in dietary supplements and herbal matrices by LC–ESI–MS and LC–UV

Gratz, Samuel R.; Flurer, Cheryl L.; Wolnik, Karen A.

doi:10.1016/j.jpba.2004.07.004

Cited by 165 publications

(117 citation statements)

References 11 publications

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“…Adulteration is an exemplary repercussion of such laxity. Well documented are instances of diuretics, stimulants, anorectics, or oxidative uncouplers contained in weight loss supplements [60][61][62][63][64][65][66][67][68][69][70][71][72][73][74], steroids in performance enhancers [75][76][77][78][79][80], and phosphodiesterase 5 inhibitors contained within male enhancement products [72,74,[81][82][83][84][85][86][87][88][89][90][91][92][93]. At least nine people died in Sweden following exposure to Kratom adulterated with Odesmethyltramadol, a potent opioid analgesic.…”

Section: Supplement Regulationmentioning

confidence: 99%

Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine

et al. 2016

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Introduction Kratom (Mitragyna speciosa), a plant native to Southeast Asia, has been used for centuries for its stimulant and opium-like effects. Mitragynine and 7-hydroxymitragynine, exclusive to M. speciosa, are the alkaloids primary responsible for Kratom's biologic and psychoactive profile, and likely contribute to its problematic use. We purchased several commercially available Kratom analogs for analysis and through our results, present evidence of probable adulteration with the highly potent and addictive plant alkaloid, 7-hydroxymitragynine. Methods A simple and sensitive LC-MS/MS method was developed for simultaneous quantification of mitragynine and 7-hydroxymitragynine in methanol extract of marketed Kratom supplements. Results We found multiple commercial Kratom products to have concentrations of 7-hydroxymitragynine that are substantially higher than those found in raw M. speciosa leaves. Conclusions We have found multiple packaged commercial Kratom products likely to contain artificially elevated concentrations of 7-hydroxymitragynine, the alkaloid responsible for M. speciosa's concerning mechanistic and side effect profile. This study describes a unique form of product adulteration, which stresses the importance of increased dietary supplement oversight of Kratom-containing supplements.

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Section: Supplement Regulationmentioning

confidence: 99%

Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine

et al. 2016

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“…Identification of the compounds was based on retention time, protonated molecular ions, and fragment ions at individually selected collision energies (CEs). The CEs were set to 5,10,15,20,25,30,35, and 40 eV, and the optimal CE was determined for each PDE-5 inhibitor.…”

Section: Resultsmentioning

confidence: 99%

“…[1][2][3][4][5] Some products have been found to be adulterated with approved PDE-5 inhibitors as well as their unapproved synthetic analogues, which contain minor structural modifications compared to the approved compounds. The presence of PDE-5 inhibitors or their analogues in herbal supplements could pose a significant risk to the public health.…”

Section: Introductionmentioning

confidence: 99%

Identification and evaluation of fragmentation pathways of PDE-5 inhibitor analogues using LC-QTOF-MS

Do¹,

Noh²,

Yoon³

et al. 2015

Analytical Science and Technology

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Phosphodiesterase type 5 inhibitors (PDE-5 inhibitors) are used in the treatment of erectile dysfunction.In recent years, a number of reports have been conducted on dietary supplements contaminated with PDE-5 analogues. In this study, 58 analogues of PDE-5 inhibitors were sorted into five groups: tadalafil, sildenafil, hongdenafil, vardenafil, and other analogues. These analogues were then evaluated using a liquid chromatographyquadrupole-time of flight mass spectrometry (LC-QTOF-MS) electrospray ionization mass method. Each compound has a unique fragmentation ion, which can be easily analyzed qualitatively. The fragmentation pathways of the analogues were elucidated based on the QTOF-MS and MS/MS data. Common ions were confirmed for each group by analyzing the structural characteristics and fragmentation pathways. Specifically, common ions were observed at m/z 169.08 and 135.04 (tadalafil analogues), m/z 311.15 and 283.12 (sildenafil analogues and hongdenafil analogues), and m/z 312.16 and 151.09 (vardenafil analogues). The advantage of this method is that the structure of unknown components can be determined by interpreting the product ions.Hence, the developed method can be used for the identification of unknown compounds. Fragmentation pathways may also aid in the detection and identification of PDE-5 inhibitor analogues.

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“…There are several methods described in the literature for SILC API determination or dosage forms by various techniques. Most of these methods are based on the high-performance liquid chromatography (HPLC) or ultra-performance liquid chromatography (UPLC) using UV-Vis or mass detectors, however, they require several pieces of expensive reagents/equipments (Gratz, Flurer, Wolnik, 2004;De Orsi et al, 2009;Song, El-Demerdash, Lee, 2012;Damiano et al, 2014;Fejos et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of alternative methods by non-aqueous acid-base titration and derivative ultraviolet spectrophotometry for quantification of sildenafil in raw material and tablets

Silva

Toledo

Vianna-Soares

2017

Braz. J. Pharm. Sci.

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Sildenafil citrate (SILC) is a potent phosphodiesterase-5 inhibitor used for erectile dysfunction and pulmonary hypertension. This study shows two simple, fast and alternative analytical methods for SILC determination by non-aqueous titration and by derivative ultraviolet spectrophotometry (DUS) in active pharmaceutical ingredient and/or dosage forms. The quantitation method of SILC active pharmaceutical ingredient by non-aqueous acid-base titration was developed using methanol as solvent and 0.1 mol/L of perchloric acid in acetic acid as titrant. The endpoint was potentiometrically detected. The non-aqueous titration method shows satisfactory repeatability and intermediate precision (RSD 0.70-1.09%). The neutralization reaction occurred in the stoichiometric ratio 1:1 in methanol. The determination of SILC active pharmaceutical ingredient or dosage forms by DUS was developed in the linear range from 10 to 40 µg/mL, in 0.01 mol/L HCl, using the first order zero-peak method at λ 256 nm. The DUS method shows selectivity toward tablets excipients, appropriate linearity (R 2 0.9996), trueness (recovery range 98.86-99.30%), repeatability and intermediate precision in three concentration levels (RSD 1.17-1.28%; 1.29-1.71%, respectively). Therefore, the methods developed are excellent alternatives to sophisticated instrumental methods and can be easily applied in any pharmaceutical laboratory routine due to simple and fast executions.Uniterms: Sildenafil citrate. Vasodilator. Derivative ultraviolet spectrophotometry. Non-aqueous acidbase titrimetry. Sildenafil citrate/quality control.

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Analysis of undeclared synthetic phosphodiesterase-5 inhibitors in dietary supplements and herbal matrices by LC–ESI–MS and LC–UV

Cited by 165 publications

References 11 publications

Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine

Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine

Identification and evaluation of fragmentation pathways of PDE-5 inhibitor analogues using LC-QTOF-MS

Development and validation of alternative methods by non-aqueous acid-base titration and derivative ultraviolet spectrophotometry for quantification of sildenafil in raw material and tablets

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