Adulteration Of Dietary Supplements Research Articles

Applications of Capillary Electrophoresis for the Detection of Adulterants in Dietary Supplements.

In recent years, the consumption of dietary supplements, particularly those incorporating plant-based ingredients, has increased greatly, driven by the perception of their natural origins and purported minimal health risks. However, one significant safety concern revolves around the adulteration of dietary supplements, wherein unscrupulous manufacturers may illegally incorporate pharmaceutical substances or their analogs into these products to achieve increased efficiency and bolster sales. This review assesses the role of capillary electrophoresis (CE) in ensuring the quality control of dietary supplement products over the past two decades. This study provides an overview of various applications of CE in analyzing dietary supplements, outlining the typical attributes of natural product analysis using CE. These analyses demonstrate the broad versatility of CE, exemplified by its diverse applications and detection modes. Moreover, the review highlights the growing prominence of CE as a separation technique in quality control, by comparison with more conventional methods like high-performance liquid chromatography (HPLC). Through this exploration, the review elucidates the pivotal role of CE in upholding the integrity and safety of dietary supplements, in connection with a landscape of evolving regulatory challenges and consumer demands.

Adulterated dietary supplements commercialized in Brazil: development of a screening method and a preliminary study of cytotoxicity

The high consumption of dietary supplements was a fundamental driver for the creation of the regulatory framework by the Brazilian governmental authorities. However, the regulatory agencies lack official low-cost methodologies to evaluate the quality of food supplements. A preliminary screening method by HPLC-DAD was proposed and validated for screening and quantification of adulterants in dietary supplements. The limits of detection and quantification were <0.11 and 0.37 µg.g−1, respectively. The method was applied for the investigation of ten unauthorized substances (spironolactone, hydrochlorothiazide, furosemide, clenbuterol, testosterone, testosterone propionate, yohimbine, vardenafil, tadalafil, and sildenafil) with a time of analysis of <5 min. Sixteen percent of the 44 samples analyzed had at least one adulterant at or above therapeutic concentrations. Subsequently, in vitro evaluations were performed of the potential cytotoxicity to evaluate the cell viability, DNA damage, determination of nitric oxide levels, and quantification of reactive oxygen species. Despite the necessity of further studies, the results indicate a relationship between the presence of adulterants in food supplements and a potential cytotoxic effect.

Proceedings of PRINCETON IV: PDE5 inhibitors and cardiac health symposium.

Prior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new data in the past decade, a fourth consensus conference on this topic was convened in Pasadena, California, on March 10 and 11, 2023. Our meeting aimed to update existing knowledge, assess current guidelines, and make recommendations for future research and practice in this area. An expert panel reviewed existing research and clinical practice guidelines. Key findings and clinical recommendations are the following: First, erectile dysfunction (ED) is a risk marker and enhancer for cardiovascular (CV) disease. For men with ED and intermediate levels of CV risk, coronary artery calcium (CAC) computed tomography should be considered in addition to previous management algorithms. Second, sexual activity is generally safe for men with ED, although stress testing should still be considered for men with reduced exercise tolerance or ischemia. Third, the safety of PDE5 inhibitor use with concomitant medications was reviewed in depth, particularly concomitant use with nitrates or alpha-blockers. With rare exceptions, PDE5 inhibitors can be safely used in men being treated for hypertension, lower urinary tract symptoms and other common male disorders. Fourth, for men unresponsive to oral therapy or with absolute contraindications for PDE5 inhibitor administration, multiple treatment options can be selected. These were reviewed in depth with clinical recommendations. Fifth, evidence from retrospective studies points strongly toward cardioprotective effects of chronic PDE5-inhibitor use in men. Decreased rates of adverse cardiac outcomes in men taking PDE-5 inhibitors has been consistently reported from multiple studies. Sixth, recommendations were made regarding over-the-counter access and potential risks of dietary supplement adulteration. Seventh, although limited data exist in women, PDE5 inhibitors are generally safe and are being tested for use in multiple new indications. Studies support the overall cardiovascular safety of the PDE5 inhibitors. New indications and applications were reviewed in depth.

A novel standard-free detection of adulteration method for sildenafil derivatives in dietary supplements.

The rapid and accurate detection of illegal adulteration of chemical drugs into dietary supplements is a big challenge in the food chemistry field. Detection of compounds without a standard reference is even more difficult; however, this is a common situation. Here in this study, a novel "standard-free detection of adulteration" (SFDA) method was proposed and phosphodiesterase-5 inhibitor derivatives were used as an example to figure out the possibility and reliability of this SFDA method. After analysis by quadrupole coupled time of flight-tandem mass spectrometry detection and multivariable statistics, six common fragment ions were chosen to indicate whether adulteration was present or not, while 20 characteristic fragment ions indicated whether adulteration was by nitrogen-containing heterocycles or by anilines. Furthermore, the quantitative methods were conducted by high-performance liquid chromatography-tandem mass spectrometry. In a word, this strategy allows for a quick determination of dietary supplement adulteration without any need for standard materials, improving the efficacy of food safety testing.

Analysis of phosphodiesterase type 5 inhibitors and analogues as adulterants in herbal dietary food supplements in Saudi market using green UPLC-MS/MS method: Assessment of the greenness and whiteness profiles

Herbal dietary supplements are popular alternatives to oral phosphodiesterase type 5 inhibitors (PDE5Is) for treating Erectile Dysfunction (ED), yet concerns arise regarding their adulteration with undeclared synthetic PDE5Is or analogues, posing health risks. The aim of this study was to develop and validate a green UPLC-MS/MS method for sensitive and rapid detection of PDE5Is and analogues in sexual enhancement herbal dietary supplements marketed in Saudi Arabia. Method validation revealed good linearity with determination coefficients (r2) ≥ 0.9990, and LODs and LOQs in the range of 0.4 – 32 ng g−1 and 1––96 ng g−1, respectively. The accuracy ranged from 80.8 % to 103.4 % while inter-day precision was ≤ 8.6 % and intra-day precision was ≤ 8.4 %. The method was successfully utilized to analyze 32 herbal dietary supplements. The results revealed that 18 samples (56.3 %) tested positive for at least one of the target analytes. Sildenafil emerged as the most frequently detected analyte, found in 15 samples (20.1 µg g−1 to 37,492 µg g−1). Tadalafil was detected in 7 samples, with concentrations ranging from 4.46 µg g−1 to 19,986 µg g−1. Yohimbine was detected in only 4 samples, while icariin was detected at lower concentrations in 3 samples. Furthermore, the method greenness and whiteness profiles were evaluated using four metrics including the Analytical Eco-Scale, Green Analytical Procedure Index (GAPI), Analytical GREEnness (AGREE) metric, and Red-Green-Blue 12 (RGB 12) metric.This study provides foundational data on the adulteration of dietary supplements in Saudi Arabia and offers insights for future interventions to promote consumer safety and awareness regarding herbal dietary supplement consumption.

Adulteration in dietary supplements: HPTLC profiling of Withania somnifera and Terminalia bellirica

In the realm of traditional medicine, (Withania somnifera), commonly known as Ashwagandha, has long been revered for its multifaceted benefits, earning it the moniker "Indian Ginseng" or winter cherry within Unani systems. Its reputation precedes it, boasting a spectrum of advantageous properties such as antiviral, antioxidant, and anti-inflammatory effects. Moreover, research suggests its potential efficacy against various cancers including breast, colon, prostate, ovarian, and lung cancer. Similarly, Terminalia bellirica, referred to as Behra, holds its own array of therapeutic potential, addressing maladies ranging from headaches to liver disorders, gastrointestinal discomforts, common colds, and constipation. However, the widespread popularity of these medicinal plants has led to concerns regarding their sustainability. Overexploitation poses a significant risk, potentially depleting these valuable resources. Compounded with this risk is the issue of adulteration or contamination, where other plant parts or species resembling the authentic herbs are utilized, compromising the safety and efficacy of the end the product. In a recent investigation, two samples each of authentic and commercial Withania somnifera and Terminalia bellirica were subjected to rigorous assessment through physiochemical, phytochemical, TLC, and HPLC chromatographic methods. Alarming findings surfaced, revealing instances of adulteration or contamination in both the Ashwagandha and Behra products. Phytochemical analyses and HPTLC profiles of various extracts unveiled the intentional or unintentional addition of undesired herbs or substitutions. These adulterants not only jeopardize the expected therapeutic outcomes but also dilute the potency and safety of the herbal medicines flooding the local markets. This study serves as a clarion call for stringent authentication measures in the procurement and utilization of herbal medicines. High-Performance Thin-Layer Chromatography (HPTLC) emerges as a reliable tool for confirming adulteration, urging stakeholders to adopt thorough authentication protocols to safeguard public health and preserve the integrity of traditional herbal remedies.

Determination of 13 potential anti-obesity agents in hair by dispersive liquid-liquid microextraction-assisted UHPLC-MS/MS

As the adulteration of dietary supplements with synthetic drugs remains a prevalent issue, the inclusion of anti-obesity agents may pose health risks, potentially leading to central nervous system or cardiovascular diseases. However, surveillance studies on the use of anti-obesity agents by the Chinese population are limited. This study aims to establish an efficient and rapid hair pretreatment method using dispersive liquid-liquid microextraction (DLLME) combined with high-speed grinding and develop a sensitive and accurate analytical method employing ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for detecting 13 potential anti-obesity agents in hair samples. Herein, hair samples were washed sequentially with 0.1% sodium dodecyl sulfate (SDS), water and acetone, and then ground at high speed using 1 mL of an extraction solution (internal standard solution-n-butanol-1.2 mol/L Na2HPO4, pH10.0, 100:400:500, v/v/v for procaterol; internal standard solution-ethyl acetate-1.2 mol/L Na2HPO4, pH8.0, 100:300:600, v/v/v for other 12 anti-obesity agents) while simultaneously performing DLLME. The developed method successfully detected 13 anti-obesity agents within 11 min, including bambuterol, clenbuterol, ractopamine, clorprenaline, formoterol, salbutamol, terbutaline, procaterol, phentermine, bupropion, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine, which improved the screening efficiency. The calibration curves exhibited good linearity of 0.025–5 ng/mg, achieving correlation coefficients of r ≥ 0.99. The lower limits of quantification (LLOQs) for the analytes were 0.025 ng/mg, demonstrating acceptable levels of accuracy and precision. Recovery rates ranged between 73.30% and 107.47% across the three concentrations of 0.075, 0.375, and 3.75 ng/mg. The validated method was successfully applied to 369 real cases and detected six analytes, including bambuterol, salbutamol, terbutaline, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine. This method offers several advantages, including simple pretreatment, high extraction efficiency, rapid extraction, solvent economy, and pollution mitigation, making it highly suitable for large-scale surveillance of usage of added anti-obesity agents.

Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health.

In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs. In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease. A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus. Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors. An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed. Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease. Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting. The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.

Nontargeted screening method for detection of illicit adulterants in dietary supplements and herbal medicines using UHPLC-QTOF-MS with fine-tuned Spec2Vec-based spectral similarity and chemical classification filter

Liquid chromatography-mass spectrometry (LC-MS) is a widely utilized technique for inspecting adulteration. Unscrupulous businesses persistently introduce novel illegal adulterants, making it necessary to develop methods to screen compounds not present in the current library. Conventional cosine similarity for mass spectral libraries matching is limited in their ability to identify structurally similar compounds. In our previous study, comparison of performance among four advanced similarity algorithms revealed that Spec2Vec exhibited the best performance in terms of both detection capability and false discovery rate, making it the chosen method for identifying illegal adulterants. However, Spec2Vec still exhibited worse performance compared to MS2DeepScore and entropy similarity in the aspects of detection capability and false discovery rate, respectively. In this study, our objective was to optimize the performance of spectral similarity for a specific compound class by fine-tuning a pretrained Spec2Vec model. Additionally, we implemented the chemical classification tool CANOPUS to address the issue of similarities in backbone structures between illegal adulterants and compounds found in herbal medicine, which can lead to false positives. We utilized glucocorticoids as potentially illicit adulterants to provide a proof-of-concept, and the results demonstrated that the fine-tuned Spec2Vec model not only exhibits a significant improvement in detection ability compared to the original model but also achieves comparable performance to MS2Deepscore. Moreover, the fine-tuned Spec2Vec model shows notably fewer false positives in comparison to MS2Deepscore. Overall, this proposed pipeline demonstrates high effectiveness and competitiveness in inspecting illegal adulterants, enhancing the analysis of large-scale MS data.

Prevalence of adulteration in dietary supplements and recommendations for safe supplement practices in sport.

The prevalence of dietary supplement use among athletes continues to rise with 60-80% of athletes often reporting current or previous use of dietary supplements. While select dietary ingredients have been shown to improve acute performance and enhance training adaptations over time, it is important to still consider the risk vs. reward for athletes before opting to consume a dietary supplement. Previous work has indicated that certain dietary supplements may pose risks for inadvertent doping, may be susceptible to mislabelling, could be banned by certain governing bodies of sport, or pose health risks for certain populations. The purpose of the current narrative review is to summarize the prevalence of adulteration in dietary sport supplement products, outline the risks of inadvertent doping for athletes, and highlight best practices regarding safe supplementation strategies. Analytical studies have found anywhere from 14 to 50% of samples analyzed from dietary supplement products have tested positive for anabolic agents or other prohibited substances. It is important for the consumer to adhere to safe supplementation strategies, which include following serving size recommendations, cross-referencing ingredient profiles with the list of prohibited substances, choosing quality products that have been verified by a third-party certification program, and being cognizant of consuming multiple dietary supplement products with overlapping ingredient profiles. Once these practices have been considered, it is reasonable for an athlete to utilize dietary supplements as a strategy to optimize performance and health, with a low risk of failing a drug test (adverse analytical finding) and experiencing adverse events.

Using stable carbon isotope ratio analysis to detect adulteration in red yeast rice dietary supplements

Red yeast rice (RYR) is marketed as a dietary supplement because it contains natural 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), including monacolin K. However, there is concern that some RYR supplements may be adulterated with the pharmaceutical drug lovastatin to enhance health claims. We have developed an optimized method to isolate monacolin K/lovastatin from complex RYR dietary supplement matrices to then test for adulteration in RYR supplements using stable carbon isotope (δ13C) analysis. Samples were initially screened for monacolin K/lovastatin using liquid chromatography with mass spectrometric detection (LC-MS). To ensure the extraction process did not affect the measured isotopic values (i.e., isotopic fractionation effects), neat lovastatin standards were spiked into two types of blank RYR matrices (powder and gel). The monacolin K/lovastatin peaks were detected using high performance liquid chromatography with ultraviolet detection (HPLC-UV) and isolated using fraction collection. Residual matrix components were removed from targeted fractions by solid phase extraction (SPE) using graphitized carbon black cartridges. The resulting isolates were then analyzed using elemental analyzer-isotope ratio mass spectrometry (EA-IRMS) to measure δ13C values. The δ13C values of the extracted lovastatin standards were compared to their respective neat lovastatin δ13C values and demonstrated negligible isotopic fractionation effects. Using this optimized clean up method and carbon isotope analysis, thirty-one samples were screened. Eight RYR dietary supplement samples had >0.8 mg/g of monacolin K/lovastatin, our minimum threshold for analyzing samples using this method. Four of these eight samples had δ13C values greater than −28.3‰, a previously proposed cutoff value for natural monacolin K, indicating likely adulteration. Additionally, five RYR powder samples were analyzed as part of a collaborative study using in-house methods from two laboratories and the data shows acceptable agreement in the δ13C values of monacolin K/lovastatin (differences ranging from ±0.02‰ to ±0.76‰). This optimized method represents a robust, reproducible procedure for detecting lovastatin adulteration in dietary supplements with minimal isotopic fractionation.

A multi-analyte screening method for the rapid detection of illicit adulterants in dietary supplements using a portable SERS analyzer

The popularity and number of dietary supplements on the health market have experienced an unprecedented boost in recent years. Simultaneously, their increased use has been accompanied by an increase in acute intoxication cases linked to the adulteration of these products with illicit and undeclared substances. In this study, a SERS-based screening methodology was developed to rapidly detect illegally added pharmaceutically active substances to dietary supplements. A portable analyzer and silver printed-SERS substrates were used to enhance the signal, requiring less than 20 min of sample preparation prior to the analysis. The method was successful in the qualitative identification of eleven out of twenty-three illicit adulterants in the dietary supplements; it could detect the target compounds at realistic adulteration levels (0.1–5.0% w/w), demonstrating the potential of SERS-based methodologies for forensic rapid screening applications. The developed method is quick, easy to use, requires no skilled technicians and little sample preparation, and allows in-situ analyses. For these reasons, it is suitable for quick screening to be performed by inspectors at customs. Moreover, the low specificity of spectroscopic methods, to which SERS belongs, would benefit the detection of newly synthesized analogues of the target adulterants, which would otherwise be more difficult using common mass spectrometry methods in absence of reference standards.

Spectroscopic determination of hydrophobic adulterant tadalafil by aptasensor based ellipsometry

Tadalafil is one of the selective phosphodiesterase type 5 inhibitors (PDE5) and serves as the active compound in drugs used for the treatment of erectile dysfunction. These PDE5 inhibitors are prescribed under medical supervision. However, cases of adulteration of dietary supplements with PDE5 inhibitors or their unapproved analogs have been reported worldwide. The presence of the PDE5 inhibitors in such supplements poses a serious health risk to consumers, particularly when combined with certain nitrate-containing drugs, as their toxic effects have not been thoroughly assessed and may result in unpredictable adverse reactions. Therefore, it is crucial to detect adulteration in these dietary supplements. However, current methods for PDE5 inhibitor detection rely on time-consuming and expensive analytical techniques, although they are sensitive. In this study, we propose an aptasensor based on ellipsometry for the detection of PDE5 inhibitors. To enhance the detection specificity for PDE5 inhibitors, we designed an aptamer with a hydrophobic pocket that incorporates a guanine base-rich region and a three-way junction. This design is particularly effective considering the poor aqueous solubility of PDE5 inhibitors. Preliminary results demonstrate that tadalafil detection in various media can be achieved within the range of 1–2000 ng/mL. The limit of detection for the active compound of tadalafil is as low as 1.82 ng/mL.

Dietary supplement adulteration - knowledge, attitudes, and practices of California health care professionals: A cross-sectional survey study

ObjectiveTo assess knowledge, attitudes, and practices surrounding dietary supplements (DS) among California health care professionals (HCPs) and assess factors contributing to the frequency with which HCPs discuss DS with patients. MethodsIn this cross-sectional study, an online questionnaire was distributed to HCPs in California from December 2021-April 2022 via professional membership email listservs. ResultsAmong 514 HCPs, overall knowledge of DS did not vary significantly by professional group, and 90% had received little to no DS education. Pharmacists (OR = 0.328, p = 0.0001) and those with less reported DS education (OR = 0.58, p = 0.0045; OR = 0.075, p = 0.0097) had a decreased likelihood of initiating conversations about DS more frequently. Females (OR = 2.5, p < 0.0001) and those with a higher knowledge score (OR = 1.2, p = 0.0297) had an increased likelihood of initiating conversations about DS more frequently. ConclusionsHCPs acknowledge the clinical significance of DS adulteration and would benefit from additional informational resources to reduce the adverse effects associated with adulterated supplements. Practice implicationsHCPs initiate more conversations about DS use when they are more informed and will gain from staying up to date on DS-related information to encourage more patient communication.

Determination of Phosphodiesterase Type-5 Inhibitors (PDE-5) in Dietary Supplements.

This study proposed a high-performance thin-layer chromatography (HPTLC) screening method to detect phosphodiesterase 5 (PDE-5) inhibitors as possible adulterant agents in various dietary supplements. Chromatographic analysis was performed on silica gel 60F254 plates using a mixture of ethyl acetate:toluene:methanol:ammonia in a volume ratio of 50:30:20:0.5 as a mobile phase. The system provided compact spots and symmetrical peaks of sildenafil and tadalafil with retardation factor values of 0.55 and 0.90, respectively. The analysis of products purchased from the internet or specialized stores demonstrated the presence of sildenafil, tadalafil, or both compounds in 73.3% of products, highlighting inadequacies and inconsistencies in the labeling, as all dietary supplements were declared to be natural. The results were confirmed using ultra-high-performance liquid chromatography coupled with a positive electrospray ionization high-resolution tandem mass spectrometry (UHPLC-HRMS-MS) method. Furthermore, in some samples, vardenafil and various analogs of PDE-5 inhibitors were detected using a non-target HRMS-MS approach. The results of the quantitative analysis revealed similar findings between the two methods, with adulterant quantities found to be similar to or higher than those in approved medicinal products. This study demonstrated that the HPTLC method is a suitable and economical method for screening PDE-5 inhibitors as adulterants in dietary supplements intended for sexual activity enhancement.

Fast screening and identification of illegal adulteration in dietary supplements and herbal medicines using molecular networking with deep-learning-based similarity algorithms.

Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is a powerful analytical tool used for adulteration inspection. Nevertheless, it is a challenging task to identify illegal adulterants that are not included in the library or are unexpected from large MS data. Molecular networking is a good tool for exploring, visualizing, and organizing MS/MS spectra, and moreover, it employs shifted peak match to calculate spectral similarity, making it capable of identifying adulteration that is not included in the library. The key of molecular networking is spectral similarity algorithms, and therefore, in this study, we compared the performance of four cutting-edge similarity algorithms, modified cosine similarity (shifted peak match), entropy similarity, and two deep-learning-based algorithms, MS2DeepScore and Spec2Vec, in building molecular networking for identification of adulteration that is not included in the library. We conducted an analysis of excluded-query-compound on all MS/MS spectra in test library and performed a large-scale false discovery rate estimation to investigate whether the spectral similarity calculated by each algorithm could represent the actual structural similarity well. The obtained results demonstrated Spec2Vec exhibited good performance in both detection capability and false discovery rate. Further comprehensive evaluation of the performance of Spec2Vec in the identification of adulteration that is not included in the library or is unexpected in different matrices and in application to real samples proved the approach studied here is a promising and powerful tool for adulterant inspection and improved the capability of analyzing large MS data.

Development of a detector tube for screening tadalafil and its analogues in adulterated sexual enhancement products.

Sexual enhancement products adulterated with phosphodiesterase 5 inhibitors (PDE-5i) pose a serious public health concern. Tadalafil and its analogues (Tds) are PDE-5i frequently detected as adulterants. In this study, a Td detector tube for the rapid detection of Tds was developed based on the color change reaction between sulfuric acid and Tds. The specificity of this test method was evaluated using 13 Tds, all of which elicited positive results. Additionally, 30 commonly found adulterants in dietary supplements, 11 active pharmaceutical ingredients of psychotropic drugs and 18 food ingredients were tested and obtained no false-positive results, except levomepromazine. The test tube accurately detected the presence or absence of Tds in 54 commercially available products. The visual detection limit was 2-50 and 5-20 μg/ml for Tds and tadalafil-spiked samples with matrix, respectively. The applicability of the developed detector tube to a semiquantitative test using digital image analyses were investigated using red, green, and blue color values. The results of the recovery test suggested that the tube test was affected by the dark-colored matrix. The results of semiquantitative analyses of tadalafil for five marketed products were consistent with the liquid chromatographic quantification results, except for the blue value. The detector tube developed in this study can facilitate with the rapid screening of Tds in adulterated sexual enhancement products.

Chemical profiling and UHPLC-QToF analysis for the simultaneous determination of anthocyanins and flavonoids in Sambucus berries and authentication and detection of adulteration in elderberry dietary supplements using UHPLC-PDA-MS

This work was initiated to develop a simple, quick, and reliable UHPLC-PDA-MS method to identify chemical markers for authentication and compare fruit samples of four elder species, Sambucus nigra, S. ebulus, S. canadensis, and S. cerulea. The UHPLC method showed an adequate separation of 11 compounds including anthocyanins, phenolic acids, and flavonoids in berries of the four Sambucus species. Quantification, detection limits, precision, accuracy as well as robustness were determined. The analysis of 55 different samples of four Sambucus species showed distinct phytochemical fingerprints. Thirty-one dietary supplements claiming to contain S. nigra berries extract were analyzed to determine authenticity. Ten (32%) of the 31 products complied with the label and contained only elderberry. The application of UHPLC-QToF provided useful information to characterize seventy-three compounds that can be used to distinguish among the four Sambucus species and also help to determine the presence of adulterants. Extracts of black rice (Oryza sativa) were identified as the main adulterants in the dietary supplements, although other undeclared ingredients such as extracts of purple carrot (Daucus carota ssp. sativus var. atrorubens) and flowers of S. nigra were also found instead of elder berry in two products. In addition to the detection of adulterated samples based on a comparison of the chemical profiles of anthocyanin and flavonoids, the developed methods can also be useful for the quality assessment of both bulk raw material and dietary supplements.

Continued Risk of Dietary Supplements Adulterated With Approved and Unapproved Drugs: Assessment of the US Food and Drug Administration's Tainted Supplements Database 2007 Through 2021.

The US Food and Drug Administration created the Tainted Dietary Supplement Database in 2007 to identify dietary supplements adulterated with active pharmaceutical ingredients (APIs). This article compares the determination of API adulteration in dietary supplements from the 10-year time period of 2007 through 2016 to the most recent 5-year period of 2017 through 2021. From 2007 through 2021, 1068 unique products were found to be adulterated with APIs. Sexual enhancement and weight loss dietary supplements are the most common products adulterated with APIs. Phosphodiesterase-5 inhibitors are commonly included in sexual enhancement dietary supplements and a single product can include up to 5 APIs. Sibutramine, a drug removed from the market due to cardiovascular adverse events, is the most included adulterant API in weight loss products, although sibutramine analogues, phenolphthalein (which was removed from the US market because of cancer risk), and fluoxetine were also included. While muscle-building dietary supplements were commonly adulterated before 2016, since 2017 no additional adulterated products have been identified. The lack of disclosure of APIs in dietary supplements, circumventing the normal procedure with clinician oversight of prescription drug use, and the use of APIs that are banned by the Food and Drug Administration or used in combinations that were never studied are important health risks for consumers.

The presence of unauthorized ingredients in dietary supplements: An analysis of the risk warning data in Korea

The Ministry of Food and Drug Safety (MFDS) has identified that numerous dietary supplements contain unapproved (hidden, undeclared, and unauthorized) ingredients that could be unsafe. The aim of this study is to summarize the presence of unapproved ingredients in dietary supplements based on the warning dataset released by the MFDS from 2010 to 2019. The warning data were extracted from the alert system on the MFDS’s website. The highest number (ratio) of products found in the dataset were marketed for sexual enhancement [770 (43.3 %)], weight-loss [690 (38.8 %)], muscular strengthening [243 (13.7 %)], or relaxing [76 (4.3 %)]. A total of 1779 products contained one or more unapproved ingredients. The most common unauthorized compounds were icariin, sildenafil, and tadalafil for sexual enhancement, yohimbine, sibutramine, and sennoside for weight loss, and yohimbine and icariin for muscular strengthening, and melatonin and 5-hydroxytryptophan for relaxing products, respectively. Unapproved ingredients continue to be identified in dietary supplements, especially those marketed for sexual enhancement or weight loss, even after warnings by regulatory authorities. The unauthorized compounds in these dietary supplements have potential adverse health effects on consumers owing to accidental misuse, overuse, interaction with other medications, underlying health conditions, or other pharmaceuticals within the supplement. Our study reviewed potential health issues concerning the main unapproved ingredients to contribute to the understanding of adulteration in dietary supplements. The result of this study can be used to elucidate adulteration trends of unapproved ingredients in dietary supplements.