Phosphodiesterase (PDE5) inhibition assay for rapid detection of erectile dysfunction drugs and analogs in sexual enhancement products

Products marketed as dietary supplements for sexual enhancement are frequently adulterated with phosphodiesterase‐5 (PDE5) inhibitors, which are erectile dysfunction drugs or their analogs that can cause adverse health effects. Due to widespread adulteration, a rapid screening assay was developed to detect PDE5 inhibitors in adulterated products. The assay employs fluorescence detection and is based on measuring inhibition of PDE5 activity, the pharmacological mechanism shared among the adulterants. Initially, the assay reaction scheme was established and characterized, followed by analysis of 9 representative PDE5 inhibitors (IC₅₀, 0.4–4.0 ng mL^–1), demonstrating sensitive detection in matrix‐free solutions. Next, dietary supplements serving as matrix blanks (n = 25) were analyzed to determine matrix interference and establish a threshold value; there were no false positives. Finally, matrix blanks were spiked with 9 individual PDE5 inhibitors, along with several mixtures. All 9 adulterants were successfully detected (≤ 5 % false negative rate; n = 20) at a concentration of 1.00 mg g^–1, which is over 5 times lower than concentrations commonly encountered in adulterated products. A major distinction of the PDE5 inhibition assay is the ability to detect adulterants without prior knowledge of their chemical structures, demonstrating a broad‐based detection capability that can address a continuously evolving threat of new adulterants. The PDE5 inhibition assay can analyze over 40 samples simultaneously within 15 minutes and involves a single incubation step and simple data analysis, all of which are advantageous for combating the widespread adulteration of sex‐enhancement products.     

Ultrasensitive determination of melamine in milk products and biological fluids by luminol-hydrogen peroxide chemiluminescence

An ultrasensitive chemiluminescence (CL) method for determination of melamine at picogram level was reported in a flow system. It was found that melamine can accelerate the electrons transferring rate of excited 3-aminophthalate with notable enhanced CL intensity of luminol-hydrogen peroxide reaction. The increased CL intensity was proportional to the concentration of melamine in the range from 2.5 to 250 pg mL⁻¹ (R² = 0.9953), with a detection limit of 0.9 pg mL⁻¹ (3σ) and the relative standard deviations lower than 5.0%. The proposed method was successfully applied to determine the melamine in liquid milk, yogurt, human urine and serum samples with the recovery of 98–105%, 93–105%, 98–105%, 97–109%, respectively.     

Adverse events associated with the use of complementary medicine and health supplements: An analysis of reports in the Singapore Pharmacovigilance database from 1998 to 2009

Context. The use of complementary and alternative medicine (CAM), particularly herbal medicine and their derived products, have been increasing. However, sporadic reports of serious adverse effects associated with the use of these products have become a source of concern. Spontaneous adverse event reporting may be used to monitor the safety of these products. Objective. The objectives of this study is to analyze and describe the patterns of adverse events associated with the use of Chinese Proprietary Medicine, other complementary medicine and health supplements (termed CAM products) in the Singapore Pharmacovigilance database from 1998 to 2009 and to highlight areas of safety concerns. Methods. Adverse events associated with CAM products reviewed by the Vigilance Branch of the Health Sciences Authority for the period 1998–2009 were collated and analyzed. The following information was extracted and collated: patient demographics, type and indication of CAM products, system-organ class affected, seriousness of the adverse event, route of administration, hospitalization status, outcome of adverse event, concomitant use of conventional medicine, adulterant testing and profession of the reporter. Results. In the period 1998–2009, 627 cases of adverse events due to CAM products were reported. Most of these 627 cases (80.2%) were found to be serious and most of the patients used CAM products for sexual performance enhancement (291, 46.4%), to relieve pain such as joint and neck pain (36, 5.9%) and for slimming purposes (27, 4.3%). Of the 627 cases, endocrine disorders constituted 22.5% and central nervous system disorders constituted 20.6%. Liver was the main organ involved in the serious cases. Twenty-two fatalities were reported and hepatotoxicity was responsible for the deaths of 10 patients during the study period. Conclusions. In conclusion, 627 adverse event reports associated with CAM products had been successfully analyzed and described. They constituted ～3.8% of the total number of adverse events reported from 1998 to 2009. Outbreaks of severe hypoglycemia in 2008 and 2009 were associated with the use of adulterated and illegal sexual performance enhancement products. Further work to confirm the hepatotoxicity of implicated CAM products is warranted. Reporting of suspected adverse events is strongly encouraged even if the causality is not confirmed because any signs of clustering will allow rapid regulatory actions to be taken. The analysis of spontaneously reported adverse events is important in monitoring the safety of CAM products and helps in the understanding of the benefits and risks associated with the use of such products.     

古代中药掺伪考

通过梳理历代主流本草发现,中药掺伪古已有之.南北朝时期以造作为主,唐代始见伪充,明清以后掺伪现象泛滥.据统计,民国以前本草著作记载的掺伪品种达76味,主要集中在贵重药、动物药和人工制品.常用掺伪手法有造作、伪充2种方式.其中涉及造作的中药有11味,而以假乱真的伪充品种高达68味.掺伪现象泛滥,迫使藿香药用部位改变,盐附子、酒制当归和蜜炙黄芪等炮制品的出现均可能与之有关.中药掺伪的根本原因是医药分家,医不识药,而商家职业操守淡漠;另外,以药物产地论优劣而不仔细辨别真伪的做法亦起到一定的消极作用.     

From the deal to the needle: Drug purchasing and preparation among heroin users in drug treatment in South London

The article uses a semi-structured interview method to assess the acquisition, preparation and use of heroin in a cohort of 114 drug users in contact with treatment services in south-east London, and examines the impact of the increase in crack availability on heroin use and preparation in this population. Seventy-six participants reported using heroin on a daily basis, involving an average of 2.8 hits and using a mean of 0.75?g on each using day. Although almost all of the sample bought their own heroin, very few were confident of assessing its quality, and the mean estimated purity level of heroin bought was 22.7%. Similarly, most of the sample believed that the heroin purchased was adulterated and, although most believed that the heroin quality was evident during the preparation stage, relatively few would ask about quality at the point of purchase, and it is apparent that the beliefs held by much of the sample about drug purity issues did not impact upon their behaviour. Seventy individuals reported the joint use of heroin and cocaine with 41 of these reporting that they used heroin to come down from the high of crack, although 17 of them reported simultaneous administration (either combined in the syringe or on the foil). The variations in patterns of behaviour identified and the lack of awareness of risk reported would suggest that there are significant implications for the development of both the harm reduction strategies for multiple drug users and for the treatment services for whom complex multiple drug use is increasingly the norm.     

Single-Laboratory Validation of a Method for the Detection and/or Quantification of Select Alkaloids in Goldenseal Supplements and Raw Materials by Reversed-Phase High-Performance Liquid Chromatography

Abstract

Quality of botanical products and raw materials is important to manufacturers, regulators, researchers, and consumers. Many modern botanical quality-assurance schemes set specifications for select phytochemicals and measure against those specifications as one determinant of quality. While numerous publications describe procedures for determining compounds of interest in plant species, few methods have been systematically evaluated for accuracy, precision, or reliability, and often the analysis of finished products is not within the scope of the method. Hydrastis canadensis. L., commonly referred to as Goldenseal, is an economically important North American medicinal plant that has been subject to adulteration in commerce. The phytochemicals of interest in the plant are the alkaloids hydrastine, berberine, and canadine. Of interest is also palmatine, an alkaloid found in potential adulterant species but not in goldenseal. In this study, goldenseal materials in raw, capsule, and tablet form, including an Echinacea/ Goldenseal combination product, were extracted with acidified water and acetonitrile and their hydrastine, berberine, canadine, and palmitine content determined by HPLC. The analytical method was optimized and evaluated in a single-laboratory validation study. Calibration curves for hydrastine and berberine were linear from 10 to 150 μ g/mL. The limits of detection for palmatine and canadine were determined to be 0.5 μ g/mL, which translates to detection of levels of 0.004% w/w in test samples. Chromatographic resolution was achieved for all analytes in an isocratic 12.5-min chromatographic run employing a binary mobile phase. Triplicate determinations performed on 10 test materials by two analysts on 3 days resulted in relative standard deviations ranging from 0.9% to 3.4%.     

A low cost smart system to analyze different types of edible Bird's nest adulteration based on colorimetric sensor array

This study was performed to develop a low-cost smart system for identification and quantification of adulterated edible bird's nest (EBN). The smart system was constructed with a colorimetric sensor array (CSA), a smartphone and a multi-layered network model. The CSA were used to collect the odor character of EBN and the response signals of CSA were captured by the smartphone systems. The principal component analysis (PCA) and hierarchical cluster analysis (HAC) were used to inquiry the similarity among authentic and adulterated EBNs. The multi-layered network model was constructed to analyze EBN adulteration. In this model, discrimination of authentic EBN and adulterated EBN was realized using back-propagation neural networks (BPNN) algorithm. Then, another BPNN-based model was developed to identify the type of adulterant in the mixed EBN. Finally, adulterated percentage prediction model for each kind of adulterate EBN was built using partial least square (PLS) method. Results showed that recognition rates of the authentic EBN and adulterated EBN was as high as 90%. The correlation coefficient of percentage prediction model for calibration set was 0.886, and 0.869 for prediction set. The low-cost smart system provides a real-time, nondestructive tool to authenticate EBN for customers and retailers.     

The hidden web and the fentanyl problem: Detection of ocfentanil as an adulterant in heroin

BackgroundThe popularization of anonymous markets such as Silk Road is challenging current drug policy and may provide a new context for old issues, such as adulteration of heroin with fentanyl derivatives. The aims of this paper are to report the presence of ocfentanil, a novel, potent, non-controlled fentanyl analog, in samples sold as heroin in the hidden web, and to summarize the effects reported by users.MethodsIn 2015, four samples allegedly bought as heroin in cryptomarkets of the hidden web were sent to Energy Control for analysis. Energy Control is a Spanish harm reduction NGO that offers anonymous drug checking with the purpose of adapting counselling to the specific substances present in the drug and monitor the drug market. Identification was performed by GC/MS and LC/MS/MS. We contacted the submitters of the samples and performed an Internet search to retrieve additional information.ResultsOne sample contained ocfentanil, caffeine and heroin. Three samples contained the aforementioned substances plus paracetamol. Two out of the four contacted users reported distinct short acting, opioid-like effects. No fora discussion could be found about the effects of ocfentanil, neither web pages nor individuals advertising the substance.ConclusionWe report the presence of a new substance detected in the hidden web as an adulterant of heroin, ocfentanil. It has short acting opioid-like effects, roughly the same potency as fentanyl, and can be injected, snorted or smoked. Severe side effects have been associated with its use, including one death. No discussion about this substance could be found in the Internet, which suggests this substance has not been sold as such. Available data about purities of drugs purchased in cryptomarkets suggest that adulteration is not a severe problem and this agrees with users’ perceptions. However, this study suggests that adulteration is a real threat not only at the street level, but also for users that buy substances in cryptomarkets, and suggest the need for harm reduction initiatives in this setting.