Chemical fingerprinting of silicone-based breast implants.

With millions of women worldwide carrying them, silicone-based breast implants represent a large market. Even though silicone breast implants already have a history of use of more than 50 years, the discussion on their safety has not yet come to an end. To improve safety assessment, regulatory authorities should have the availability of a set of tests to be able to determine parameters of implant identity and quality. Therefore, the gels and envelopes of various brands and types of silicone-based breast implants have been subjected to infrared, Raman and NMR spectroscopy. We show that by using a combination of complementary spectroscopic techniques breast implants of various origins can be distinguished on typical chemical hallmarks. It was found that typical silicone-based implants display a surplus of vinyl signals in the gel, cyclosiloxane impurities are tolerable at low levels only and a barrier layer is present in the implant envelope. The techniques presented here and the results obtained offer a good starting point for market surveillance studies.

Active pharmaceutical ingredients detected in herbal food supplements for weight loss sampled on the Dutch market.

Herbal food supplements claiming to reduce weight may contain active pharmacological ingredients (APIs) that can be used for the treatment of overweight and obesity. The aim of this study was to determine whether herbal food supplements for weight loss on the Dutch market contain APIs with weight loss properties. Herbal food supplements intended for weight loss (n = 50) were sampled from August 2004 to May 2013. An HPLC-DAD-MS/MS method was used to screen for the presence of the APIs in herbal supplements. In 24 samples the APIs sibutramine, desmethylsibutramine (DMS), didesmethylsibutramine (DDMS), rimonabant, sildenafil and/or the laxative phenolphthalein were identified 41 times. The presence of these APIs was, however, not stated on the label. The potential pharmacological effects of the detected APIs were estimated using data from reported effective doses of approved drugs. Use of 20 of the 24 herbal food supplements may result in potential pharmacological effects. Furthermore, risk assessment of phenolphthalein, a suspected carcinogen and found to be present in 10 supplements, based on the margin of exposure (MOE) approach, resulted in MOE values of 96-30,000. MOE values lower than 10,000 (96-220) were calculated for the daily intake levels of four out of these 10 supplements in which phenolphthalein was found. However, taking into account that weight loss preparations may be used for only a few weeks or months rather than during a lifetime, MOE values may be two to three orders of magnitude higher. The current study shows that the use of food supplements with sibutramine, DMS, DDMS and/or phenolphthalein could result in pharmacological effects.

A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events.

Food supplements are regularly found to contain pharmacologically active substances. Recently, the food supplement Dexaprine was removed from the Dutch market because it was associated with severe adverse events. Reports to the Dutch Poisons Information Center (DPIC) showed that ingestion of as little as half a tablet caused several cases of nausea, agitation, tachycardia, and palpitations and even one case of cardiac arrest. The remaining tablets of four patients were sent in by different healthcare professionals. Analysis by ultra-performance liquid chromatography quadrupole time of flight mass-spectrometry (UPLC-QTOF-MS) confirmed the presence of synephrine, oxilofrine, deterenol, yohimbine, caffeine, and theophylline. Two more compounds were found which were tentatively identified as ß-methyl-ß-phenylethylamines. This incident is only the next in a series of similar incidents involving dietary supplements with (undeclared) active substances that are either unsafe or have no known safety profile.

Capsule shells adulterated with tadalafil.

Following a health complaint a food supplement was brought in for analysis on the suspicion of being adulterated with a synthetic drug substance. When the capsule content did not show evidence of adulteration, the capsule shell was investigated. Using HPLC-DAD and HPLC-MS the capsule shell was found to contain 2.85 mg of the erectile dysfunction drug tadalafil. Using microscopy and RAMAN spectroscopy the presence of tadalafil was shown throughout the gelatine matrix as particles and dissolved into the matrix. The adulteration is probably carried out by adding tadalafil powder to a gelatine jelly in the manufacturing of the capsules shells. Because this technique may also be used for other drug substances, capsules shells should be considered a vehicle for hiding drug substances in general.

Assessment of health claims, content, and safety of herbal supplements containing Ginkgo biloba.

BACKGROUND: European Regulation 1924/2006 states that all health claims made on foods need to be substantiated scientifically. OBJECTIVE: To apply the PASSCLAIM criteria for the scientific substantiation of health claims on foods to herbal supplements containing Ginkgo biloba. Evaluation of three selected claimed health effects for G. biloba (improvement of blood circulation, improvement of symptoms of old age, and improvement of memory) was achieved through review of publicly available scientific data. A total of 35 human intervention studies were evaluated. Commercially available products claimed to contain mainly G. biloba (N=29) were randomly sampled in the Netherlands and analyzed for their content on ginkgo extract. Also, a toxicological risk assessment was performed. RESULTS: The three selected health claims investigated could not be substantiated. This was mainly because of a lack of data from studies in healthy volunteers. In most studies results performed with a 24% standardized G. biloba extract were described. However, our chemical analysis showed that 25 of the 29 sampled products did not contain the required minimum 24% standardized extract. Moreover, in most preparations the content of substances typical for G. biloba did not conform to what was declared on the label. Since toxicity data for G. biloba are very limited, a safety limit could not be established. CONCLUSIONS: Evidence is lacking for three health claims of herbal products with G. biloba. Neither safety nor efficacy can be guaranteed at the recommended daily dose. The multidisciplinary approach described in this paper provides good insight into issues that are relevant for the evaluation of health claims for herbal food supplements.

Designer drugs in herbal aphrodisiacs.

In the presented case three herbal aphrodisiacs (Libidfit, Satibo and Viamax) were investigated for the presence of regular pharmaceuticals against erectile dysfunction. However, high-performance liquid chromatography with diode array detection and mass spectrometry (HPLC-DAD-MS) and nuclear magnetic resonance (NMR) analyses revealed the presence of ingredients, having a molecular structure strongly resembling those of sildenafil (Viagra) and vardenafil (Levitra). The health risk posed by these analogous substances is high because they were found to be potent phosphodiesterase 5 (PDE5) inhibitors used in pharmacologically relevant quantities having no known safety profile. Based on structural and functional analogy these analogs represent a new class of designer drugs and should be taken off the market for being unapproved drug substances. In the Libidfit court case this was done successfully, setting a precedent.

Detection of counterfeit Viagra with Raman spectroscopy.

During the last few years, counterfeiters have become increasingly sophisticated by falsifying drugs and making them look identical to genuine tablets. In this paper, Raman spectroscopy is proposed as a fast and reliable method for the detection of counterfeit Viagra tablets. This technique can easily differentiate genuine from counterfeit tablets without the need of sample preparation. In total 18 tablets were analysed which all contained the active ingredient sildenafil, but different excipients were used, as could be observed in the Raman spectra between 1150 and 700 cm(-1). So, the spectra could be divided into genuine or counterfeit. Additionally, principal component analysis (PCA), combined with hierarchical cluster analysis (HCA), was used to establish an automated approach for the discrimination of counterfeit from genuine Viagra tablets. Raman spectroscopy, combined with principal components analysis, could be used in the future by customs or in the field to identify counterfeit tablets on the spot without involvement of trained chemists.