Discovery of minor quality evaluation marker compounds for Chinese patent medicine products using a two-leveled metabolomics strategy.

Chinese patent medicines (CPMs) are popularly used in clinical practice. Though the composition is complex, the quality of CPM is usually evaluated by the contents of a few main compounds. In this study, a two-leveled metabolomics strategy was proposed to discover minor marker compounds for different CPM products. Zhenqi Fuzheng (ZQFZ) granule was studied an example, where 15 batches from 3 producers were analyzed. The samples were separated using UHPLC on an Acquity UPLC® HSS T3 column, and then detected using Q-Orbitrap-MS. In the first level, 1475 common peaks were extracted and 95 compounds were identified using diagnostic ions and a homemade database. In the second level, the data were subjected to a two-way hierarchical clustering analysis and screened by variable importance value. In total 14 marker compounds were discovered which were responsible for the grouping of different ZQFZ products. Echinacoside (22), oleoside (13), loganic acid (5), salidroside (7), ligustrosidic acid (42), 6α-hydroxygeniposide (28), and oleoside 11-methyl ester (15) could be used to reflect the quality difference for ZQFZ granule products. The proposed strategy could also contribute to the discovery of quality control markers for other CPMs.

Certified food dyes in over the counter medicines and supplements marketed for children and pregnant women.

Food, Drug, & Cosmetic (FD&C) dyes are synthetic color additives used in food, prescription drugs and over-the-counter medicines (OTCs). Consumption of FD&C dyes has been associated with neurobehavioral behavior in some children. The amount of dye used in commercial products is proprietary, making it difficult to assess dietary intake and determine exposure in children. To date, no studies have examined FD&C dyes in OTCs or vitamins in the United States. To address this, FD&C Red No. 40, Yellow No. 5, Yellow No. 6, Blue No. 1, and Blue No. 2 levels were measured in prenatal vitamin tablets, children's chewable and gummy vitamins, pain reliever tablets and syrups, and cough/cold/allergy tablets and syrups. Dyes were isolated using solid phase extraction (SPE) and quantified by high performance liquid chromatography (HPLC). Dye levels varied between products with highest levels in pain reliever and cough/cold/allergy syrups. Significant variability was observed within some brands. Degradation of Red No. 40, Blue No. 1, and Yellow No. 6 was observed in the vitamin gummies. Intake of FD&C Red No. 40 is two times the US FDA ADI (accepted daily intake) for some children's pain reliever syrups and almost three times the US FDA ADI for some cough/cold/allergy syrups.

Evaluation of commercially available meth-deterrent pseudoephedrine hydrochloride products.

Pseudoephedrine (PSE) extracted from its dosage forms can be used as the starting material to prepare methamphetamine by drug abusers. Recently, some pseudoephedrine drug products marketed under the over the counter (OTC) monograph have been promoted as 'meth-deterrent'. The goal of this investigation was to evaluate the extraction and dissolution of these product against controls of non-meth-deterrent products of pseudoephedrine. Immediate release (IR) PSE OTC Product-C, Product-D and Product-E with meth-deterrent claim on their packaging were selected for this study. Accordingly, OTC IR PSE tablet Product-A and OTC extended release (ER) PSE tablet Product-B, with no meth-deterrent claims, were used as controls. The extraction studies were performed on intact tablets or capsules and on manipulated products employing water, ethanol and 0.l N HCl as solvents. The extraction studies were also performed in water at elevated temperatures by heating the water in an oven and in a microwave. The dissolution studies were performed in water and 0.1 N HCl. The amount of PSE extracted from Product-C was found similar to the amount extracted from the non-meth-deterrent control Product-A. The amount of PSE extracted from Product-D and Product-E was found lower than the amount extracted from control Product-A under the conditions studied. Product-A, Product-B, and Product-C met their respective dissolution acceptance criteria. The IR Products D and E released less than 50% drug in 12 h and did not meet either IR or ER PSE tablet USP dissolution acceptance criteria. In summary, the extraction of Product-C was found to be high (approximately 85% in 30 min) and was similar in extraction to the control Product-A. The extraction of Product-D and Product-E was found less than the extraction of control Product-A. Also, Product-D and Product-E did not exhibit complete drug release. This study showed that PSE can be extracted from Product D and Product E.

Direct preparation of a graphene oxide modified monolith in a glass syringe as a solid-phase extraction cartridge for the extraction of quaternary ammonium alkaloids from Chinese patent medicine.

Packed cartridges have been widely used in solid-phase extraction. However, there are still some drawbacks, such as they are blocked easily and the method is time-consuming. In view of the advantages of monoliths, a monolithic extraction material has been directly synthesized in a glass syringe without any gap between the monolith and syringe inner wall. The monolithic syringe was modified with graphene oxide by loading graphene oxide dispersion onto it. The content of graphene oxide and the surface topography of the monolith have been evaluated by elemental analysis and scanning electron microscopy, respectively, which confirmed the successful modification. This prepared graphene oxide-modified monolithic syringe was directly used as a traditional solid-phase extraction cartridge. As expected, it shows good permeability and excellent capability for the extraction of quaternary ammonium alkaloids. The sample loading velocity (1-6 mL/min) does not affect the recovery. Under the optimal conditions, good linearities (R = 0.9992-0.9998) were obtained for five quaternary ammonium alkaloids, and the limits of detection and quantification were 0.5-1 and 1-2 µg/L, respectively. The proposed method was successfully applied for the analysis of quaternary ammonium alkaloids in Chinese patent medicine.

Paeonifiorin sulfonate as a characteristic marker for specifically inspecting Chinese patent medicine Liu-Wei-Di-Huang-Wan contained sulfur-fumigated Moutan Cortex.

Sulfur fumigation can induce chemical transformation of bioactive components, consequently the alteration of bioactivities or even toxicities of medicinal herbs. Inspecting Chinese patent medicines (CPM) contained sulfur-fumigated constituent herbs is crucial for ensuring the safety and efficacy of CPM. Paeonifiorin sulfonate is a sulfur-fumigation induced compound of Moutan Cortex (MC), one of the main constituent herbs of a commonly used CPM Liu-Wei-Di-Huang-Wan (LWDHW). Herein, we investigated the approach of paeonifiorin sulfonate as a characteristic marker for specifically inspecting LWDHW potentially contained sulfur-fumigated MC (SFMC). First, mimic LWDHW samples contained SFMC (SFMC-LWDHW) and non-fumigated MC (NFMC-LWDHW) were prepared respectively. Second, an LC-MS method was developed and validated to qualitatively and quantitatively determine paeonifiorin sulfonate in the mimic LWDHW samples. Third, the established method was applied to analyze the commercial LWDHW samples. The results showed that paeoniflorin sulfonate could only be detectable in SFMC-LWDHW, but not in NFMC-LWDHW samples. The CPM matrix could enhance the response of paeoniflorin sulfonate in mass spectrometry analysis. In addition, the LOQ, linearity, precision, accuracy and stability were also demonstrated to be acceptable for quantifying paeoniflorin sulfonate in LWDHW. Commercial samples analysis indicated that paeoniflorin sulfonate were detectable in 9 of 10 commercial LWDHW samples, with the content varied between 105.53µg/g and 438.61µg/g. All the results suggested that paeoniflorin sulfonate could be used as a characteristic and reliable chemical marker for specifically inspecting commercial LWDHW contained SFMC. This study also provides a new strategy for the quality control of other CPMs potentially produced from sulfur-fumigated constituent herbs.

A Nucleotide Signature for the Identification of Angelicae Sinensis Radix (Danggui) and Its Products.

It is very difficult to identify Angelicae sinensis radix (Danggui) when it is processed into Chinese patent medicines. The proposed internal transcribed spacer 2 (ITS2) is not sufficient to resolve heavily processed materials. Therefore, a short barcode for the identification of processed materials is urgently needed. In this study, 265 samples of Angelicae sinensis radix and adulterants were collected. The ITS2 region was sequenced, and based on one single nucleotide polymorphism(SNP) site unique to Angelica sinensis, a nucleotide signature consisting of 37-bp (5'-aatccgcgtc atcttagtga gctcaaggac ccttagg-3') was developed. It is highly conserved and specific within Angelica sinensis while divergent among other species. Then, we designed primers (DG01F/DG01R) to amplify the nucleotide signature region from processed materials. 15 samples procured online were analysed. By seeking the signature, we found that 7 of them were counterfeits. 28 batches of Chinese patent medicines containing Danggui were amplified. 19 of them were found to contain the signature, and adulterants such as Ligusticum sinense, Notopterygium incisum, Angelica decursiva and Angelica gigas were detected in other batches. Thus, this nucleotide signature, with only 37-bp, will broaden the application of DNA barcoding to identify the components in decoctions, Chinese patent medicines and other products with degraded DNA.

Authentication of Schisandra chinensis and Schisandra sphenanthera in Chinese patent medicines.

Authentication of species is crucial for ensuring the safety and efficacy of herbal medicines. The fruits of Schisandra chinensis and S. sphenanthera have been used for the same traditional Chinese drug, Wuweizi, but are found to be quite different according to their constituents, pharmacological effects, and qualities. These two fruits have been recorded as Schisandrae Chinensis Fructus (Wuweizi) and Schisandrae Sphenantherae Fructus (Nan-wuweizi), respectively, by Chinese Pharmacopoeia, 2000 edition. However, Nan-wuweizi is often found to be taken as Wuweizi in some Chinese patent drugs intentionally or by mistake because of its lower price and similar characteristics to Wuweizi. In this study, the selection and validation of special chemical markers for the identification of Schisandra species were established by HPLC-DAD-MS profiling analysis. Simple TLC and HPLC methods were proposed for the accurate determination of Nan-wuweizi from Wuweizi in Chinese patent medicines, using schisandrin and anwulignan as the identifying markers for Wuweizi and Nan-wuweizi, respectively. Through the establishment of a statistical model, adulterated or misused ratios of Nan-wuweizi in Wuweizi (w/w), as well as in Fenghan Kesou pills, can be determined. The limit of detection of Nan-wuweizi in a mixture (w/w) using both TLC and HPLC methods is 5% (mixed crude drugs of 50mg and 5g in a 1000g prescribed amount). The constructed statistical model relating the HPLC peak area ratio (anwulignan/schisandrin) and adulteration ratio is suitable for mixed crude drugs and Fenghan Kesou pills, and the two fitting equations have a good correlation (r=0.9979). Furthermore, 36 commercial Chinese patent medicines containing Wuweizi or Nan-wuweizi according to their labels were checked by these methods, and Nan-wuweizi was detected in Renshen Wuweizi Granules and Fenghan Kesou Pills. The ratios of Nan-wuweizi in these mixtures (w/w) were 100:0 for both, which does not comply with the statutory prescription. This study provided a simple and reliable method to prevent the adulteration or misuse of Nan-wuweizi in crude drugs and patent medicines of Wuweizi.

[Which one is more important, raw materials or productive technology?--a case study for quality consistency control of Gegen Qinlian decoction].

To investigate the effect of Chinese medicine raw materials and production technology on quality consistency of Chinese patent medicines with Gegen Qinlian decoction as an example, and establish a suitable method for the quality consistency control of Chinese patent medicines. The results showed that the effect of production technology on the quality consistency was generally not more than 5%, while the effect of raw materials was even more than 30%, indicating that the effect of raw materials was much greater than that of the production technology. In this study, blend technology was used to improve the quality consistency of raw materials. As a result, the difference between the product produced by raw materials and reference groups was less than 5%, thus increasing the quality consistence of finished products. The results showed that under the current circumstances, the main factor affecting the quality consistency of Chinese patent medicines was raw materials, so we shall pay more attention to the quality of Chinese medicine's raw materials. Finally, a blend technology can improve the quality consistency of Chinese patent medicines.

[Summary and analysis of safety warning on clinical application of anti-cold Chinese patent medicine preparations].

In China, many surveys have shown that most people do not have a correct understanding about cold and administration of anti-cold Chinese patent medicine preparations. The author conducted a systematic summary and analysis on the actual application of anti-cold Chinese patent medicine preparations as well as the warning on safe application of anti-cold Chinese patent medicine preparations in Clinical Medication Information of China Pharmacopoeia, in the expectation of reducing the blind application of anti-cold Chinese patent medicine preparations and providing traditional Chinese medicine pharmacists new ideas in monitoring the safe application of exterior syndrome-relieving Chinese patent medicine preparations.

Simultaneous quantitation of five Panax notoginseng saponins by multi heart-cutting two-dimensional liquid chromatography: Method development and application to the quality control of eight Notoginseng containing Chinese patent medicines.

Current China Pharmacopoeia (ChP) standards employ diversified and case-dependent assay methods to evaluate the quality of different Chinese patent medicines (CPMs) that contain Panax notoginseng as the monarch drug. These conventional, HPLC-based approaches, utilizing a complex sample preparation procedure, can easily result in low analytical efficiency and possible component loss. Here, a "monomethod-heterotrait matrix" (MHM) strategy is proposed, that is, developing a universal multi heart-cutting two-dimensional liquid chromatography (MHC-2D-LC) approach that facilitates the simultaneous quantitation of five P. notoginseng saponins (noto-R1, Re, Rg1, Rb1, and Rd) in eight different CPMs. The MHC-2D-LC system was constructed on a dual-gradient liquid chromatography instrument equipped with a Poroshell SB C18 column and a Zorbax SB-Aq column for respective (1)D and (2)D separation. Method validation was performed in terms of specificity, linearity (r(2) and F-test), intra-/inter-day precision (0.4-7.9%), stability (1.2-3.9%), and recovery (90.2-108.7%), and the LODs and LOQs (loaded masses) of the five analytes varied between 4.0-11.0ng and 6.0-33.0ng, respectively. The validated MHC-2D-LC approach was subsequently applied to quantify the five saponins in thirty batches of different CPMs. The method demonstrated superiority over the current ChP assay methods in respect of specificity (avoiding co-elution), resolution (Rs>1.5), sample preparation (easy-to-implement ultrasonic extraction without repeated re-extraction), and transfer rate (minimum component loss). This is the first application of an MHC-2D-LC method for the quantitative assessment of the constituents of CPMs. The MHM approach represents a new, strategically significant methodology for the quality control of CPMs that involve complex chemical matrix.

Discriminatory components retracing strategy for monitoring the preparation procedure of Chinese patent medicines by fingerprint and chemometric analysis.

Chinese patent medicines (CPM), generally prepared from several traditional Chinese medicines (TCMs) in accordance with specific process, are the typical delivery form of TCMs in Asia. To date, quality control of CPMs has typically focused on the evaluation of the final products using fingerprint technique and multi-components quantification, but rarely on monitoring the whole preparation process, which was considered to be more important to ensure the quality of CPMs. In this study, a novel and effective strategy labeling "retracing" way based on HPLC fingerprint and chemometric analysis was proposed with Shenkang injection (SKI) serving as an example to achieve the quality control of the whole preparation process. The chemical fingerprints were established initially and then analyzed by similarity, principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) to evaluate the quality and to explore discriminatory components. As a result, the holistic inconsistencies of ninety-three batches of SKIs were identified and five discriminatory components including emodic acid, gallic acid, caffeic acid, chrysophanol-O-glucoside, and p-coumaroyl-O-galloyl-glucose were labeled as the representative targets to explain the retracing strategy. Through analysis of the targets variation in the corresponding semi-products (ninety-three batches), intermediates (thirty-three batches), and the raw materials, successively, the origins of the discriminatory components were determined and some crucial influencing factors were proposed including the raw materials, the coextraction temperature, the sterilizing conditions, and so on. Meanwhile, a reference fingerprint was established and subsequently applied to the guidance of manufacturing. It was suggested that the production process should be standardized by taking the concentration of the discriminatory components as the diagnostic marker to ensure the stable and consistent quality for multi-batches of products. It is believed that the effective and practical strategy would play a critical role in the guidance of manufacturing and help improve the safety of the final products.

Over the counter drugs (and dietary supplement) exercise: a team-based introduction to biochemistry for health professional students.

For successful delivery of basic science topics for health-professional students, it is critical to reduce apprehension and illustrate relevance to clinical settings and everyday life. At the beginning of the Biochemistry course for Physician Assistants, a team-based assignment was designed to develop an understanding of the mechanism of action, effectiveness, and toxicity of five common over the counter (OTC) drugs and dietary supplements, and place these familiar medicines in a political and historical context. The objectives of this exercise were to stimulate interest in biochemistry; to provide basic information on enzymes and enzyme inhibitors related to these drugs to be expanded upon later in the course; and to encourage active and interactive learning. Teams of five students were formed, and each student was given an information sheet on aspirin, alpha-galactosidase, orlistat, dextromethorphan, or simvastatin, a low dose statin, which was previously available without prescription at pharmacies in the UK. After each member of the team acquired information on one OTC drug/dietary supplement by reading an assigned information sheet, the team was asked to go through a series of questions, and then submit answers to a quiz as a group. A high rate of success on the quiz, an overwhelmingly positive response on formal course evaluations, and enthusiastic exchanges during class suggested this team-based session accomplished its goals.

Adulteration of purported herbal and natural sexual performance enhancement dietary supplements with synthetic phosphodiesterase type 5 inhibitors.

INTRODUCTION: Many products labeled "herbal" or "all natural" (herbal/natural) that claim to enhance sexual performance and imply use for the treatment of erectile dysfunction (ED) are marketed as over-the-counter (OTC) dietary supplements. However, adulteration with undeclared phosphodiesterase type 5 (PDE5) inhibitors appears widespread. AIM: To assess the availability, cost, origin, categorical content, and adulteration with PDE5 inhibitors of purported herbal/natural OTC dietary supplements claiming to naturally enhance sexual performance. METHODS: Pfizer Global Security coordinated sample collection (all from convenience stores and filling stations in two U.S. metropolitan areas except for seven from U.S. Customs seizures) and liquid chromatography/mass spectrometry examination. MAIN OUTCOME MEASURE: Adulteration with synthetic PDE5 inhibitors. RESULTS: Ninety-one samples labeled as 58 distinct products and priced from $2.99 to $17.99 were evaluated. Origin/manufacture was claimed as United States (n = 62), apparently Asian (n = 15), and not clearly identified (n = 14). Although no sample claimed to include synthetic substances, 74 (81%) contained PDE5-inhibitor pharmaceutical ingredients, including tadalafil and/or sildenafil (n = 40, of which 18 contained >110% of the highest approved drug product strength) or PDE5-inhibitor analogs (n = 34). Pronounced heterogeneity of contents between samples within individual products indicated minimal quality control during manufacture. Labeling was inadequate (e.g., lacking lot number and/or expiry date) for 17 products (23 samples) and inconsistent between samples within a given product (e.g., in manufacturer, lot number, and/or expiry date) for seven of 17 products having multiple samples. Only 14 samples warned against concomitant nitrate use. CONCLUSIONS: Ethical pharmaceutical companies are concerned for an unsuspecting public when their products are counterfeited, mislabeled, and illegally offered for sale in an unsafe manner. Because of the dangers of adulteration with synthetic PDE5 inhibitors, absent safety warnings, and lack of quality or consistent manufacture, men with ED unknowingly risk their health by using OTC herbal/natural products that claim to enhance sexual performance.

Potential toxicity of caffeine when used as a dietary supplement for weight loss.

BACKGROUND: Caffeine is added to dietary supplements to increase energy and suppress appetite. Many people take dietary supplements for weight loss. Patients may be unaware that supplements can contain caffeine, even if caffeine is not listed as an ingredient. Commonly used herbal dietary supplement ingredients, such as guarana, are natural sources of caffeine. OBJECTIVE: To describe a case of possible caffeine-induced seizure in a patient taking an over-the-counter weight loss supplement. CASE REPORT: A previously healthy 38-year-old female experienced blurring of vision and a new onset grand mal seizure. The patient had a two-month history of taking the dietary supplement, Zantrex - 3™. Zantrex - 3™ is advertised as a weight loss supplement which may provide rapid weight loss and extreme energy in one "power packed pill." CONCLUSIONS/SUMMARY: After discontinuation of Zantrex - 3™, the patient experienced no further seizure activity. Outpatient follow up at 2 and 6 weeks was noncontributory with follow up MRI and EEG both within normal limits.

Heavy metal contaminants in yerberia shop products.

Complementary and alternative medications, including the use of herbal medications, have become quite popular in the USA. Yerberias are found throughout the southwest and specialize in selling Hispanic herbal products. The products sold in these stores are not regulated by any governmental agency. Previous reports have found Ayurvedic medications contain high levels of lead, mercury, and arsenic. The primary purpose of this study is to examine the prevalence of heavy metal contaminants sold at Yerberia stores in the southwest. Yerberias in the Phoenix, Arizona area were identified via search of an on-line search engine using the words "Yerberia Phoenix." Every second store was selected, and products were purchased using a standard script. The products were subsequently analyzed for mercury, lead, and arsenic. The main outcome is the prevalence of heavy metal content in over-the-counter "cold" medications purchased at a Yerberia. Twenty-two samples were purchased. One product contained pure camphor (2-camphone) and was subsequently not further analyzed. Of the 21 samples analyzed, lead was found in 4/21 (19.4 %). Arsenic and mercury were in 1/21 (4.8 %) each. Because two samples contained two heavy metals, the total prevalence of heavy metals was 4/21 (19.4). Heavy metal contaminants are commonly encountered in over-the-counter herbal "cold" medications purchased at Yerberias in the southwest.

DNA based identification of medicinal materials in Chinese patent medicines.

Chinese patent medicines (CPM) are highly processed and easy to use Traditional Chinese Medicine (TCM). The market for CPM in China alone is tens of billions US dollars annually and some of the CPM are also used as dietary supplements for health augmentation in the western countries. But concerns continue to be raised about the legality, safety and efficacy of many popular CPM. Here we report a pioneer work of applying molecular biotechnology to the identification of CPM, particularly well refined oral liquids and injections. What's more, this PCR based method can also be developed to an easy to use and cost-effective visual chip by taking advantage of G-quadruplex based Hybridization Chain Reaction. This study demonstrates that DNA identification of specific Medicinal materials is an efficient and cost-effective way to audit highly processed CPM and will assist in monitoring their quality and legality.

Simultaneous determination of synephrine, arecoline, and norisoboldine in Chinese patent medicine Si-Mo-Tang oral liquid preparation by strong cation exchange high performance liquid chromatography.

CONTEXT: Chinese patent medicine Si-Mo-Tang oral liquid preparation (SMT) is composed of Aucklandia luppa Decne (Compositae), Citrus aurantium Linn (Rutaceae), Lindera aggregata (Sims) Kosterm (Lauraceae), and Areca catechu Linn (Arecaceae). Studies of SMT have been impeded due to the lack of quality control methods. OBJECTIVE: This study aimed to simultaneously determine three alkaloids including synephrine, arecoline, and norisoboldine in SMT for the first time. MATERIALS AND METHODS: A strong cation exchange (SCX) high performance liquid chromatography (HPLC) method was developed to simultaneously determine synephrine, arecoline, and norisoboldine in SMT, and was compared with ion-pairing chromatography using regular reversed-phase chromatography columns. System suitability parameters of synephrine, arecoline, and norisoboldine using the SCX chromatography column were investigated. RESULTS: Results demonstrated that good separations were achieved on an Agilent SCX (250 × 4.6 mm, 5 µm) column at 35 °C. The mobile phase consisting of methanol-0.2% phosphoric acid was delivered at a constant flow of 1.0 mL min(-1) and the eluent was monitored at 215 nm. The HPLC method showed good linearity for the examined concentration ranges of 2.55-255.0, 1.30-208.0, and 2.06-201.6 µg mL(-1) for synephrine, arecoline, and norisoboldine, respectively. The limits of quantification (S/N = 10) were 2.55, 1.30, and 2.06 µg mL(-1), the limits of detection (S/N = 3) were 1.53, 0.78, and 1.21 µg mL(-1), and average recoveries were 98.99, 95.63 and 99.04%, respectively, for synephrine, arecoline, and norisoboldine. DISCUSSION AND CONCLUSION: This method has been successfully applied to determine synephrine, arecoline, and norisoboldine in Chinese patent medicine SMT.

Diethylene glycol in health products sold over-the-counter and imported from Asian countries.

Diethylene glycol (DEG), a chemical that has been implicated in multiple medication-associated mass poisonings, can result in renal and neurological toxicity if ingested. Three previous such mass poisonings implicated Chinese manufacturers as the origin of contaminated ingredients. No literature exists on potential DEG or triethylene glycol (TEG), a related compound, contamination of health products imported from Asian countries to the USA. Our primary objective was to quantitatively assess the amount of DEG present in a convenience sampling of these health products. The study's secondary objectives were to: (1) evaluate for, and quantify TEG levels in these samples; (2) compare DEG and TEG levels in these products directly to levels in medications implicated in previous similar mass poisonings; and (3) to estimate DEG dose (in mg/kg) based on the manufacturer's instructions and compare these values to toxic doses from past mass poisonings and the literature. A quantitative assessment of DEG and TEG was performed in a convenience sampling of over-the-counter health products imported from Asian countries. Results were converted to volume to volume (v/v) % and compared with DEG levels in medications implicated in previous mass poisonings. Estimated doses (based on the manufacturer's instructions) of each product with detectable levels of DEG for a 70 kg adult were compared to toxic doses of DEG reported in the literature. Seventeen of 85 (20%) samples were not able to be analyzed for DEG or TEG due to technical reasons. Fifteen of 68 (22%) samples successfully tested had detectable levels of DEG (mean, 18.8 µg/ml; range, 0.791-110.1 µg/ml; and volume to volume (v/v) range, 0.00007-0.01%). Two of 68 (3%) samples had TEG levels of 12.8 and 20.2 µg/ml or 0.0012% and 0.0018% TEG v/v. The product with the highest DEG% by v/v was 810 times less than the product involved in the Panama DEG mass poisoning (8.1%). The lowest reported toxic dose from a past DEG mass poisoning (14 mg/kg) was more than 150 times higher than the highest daily dose estimated in our study (0.09 mg/kg). Sixty-eight of 85 (80%) samples were able to be successfully analyzed for DEG and TEG. DEG and TEG were detectable in 15/68 (22%) and 2/68 (3%) samples, respectively. Based on current standards, these levels probably do not represent an acute public health threat. Additional research focusing on why DEG is found in these products and on the minimum amount of DEG needed to result in toxicity is needed.

Echinacea and trypanasomatid parasite interactions: growth-inhibitory and anti-inflammatory effects of Echinacea.

CONTEXT/OBJECTIVE: Herbal preparations derived from various species and parts of Echinacea (Asteraceae) have been advocated for various medical applications, as a result of the many antimicrobial and immunomodulatory activities attributed to them. MATERIALS AND METHODS: In order to investigate their effects on parasites, four preparations of Echinacea, with distinct chemical compositions, were evaluated for growth inhibition of three species of trypanosomatids: Leishmania donovani, Leishmania major, and Trypanosoma brucei. In addition one Echinacea preparation was tested for anti-inflammatory activity in cell culture models designed to measure pro-inflammatory cytokines induced by L. donovani. RESULTS AND DISCUSSION: All Echinacea preparations inhibited growth of the organisms, though with different relative potencies, and in some cases morphological changes were observed. However, there was no obvious correlation with the composition of the marker compounds, alkylamides, caffeic acid derivatives, and polysaccharides. L. donovani stimulated the production of the pro-inflammatory cytokines IL-6 and IL-8 in human bronchial epithelial cells and in human skin fibroblasts, but in both cases the standardized ethanol extract of E. purpurea (L.) Moench (Echinaforce) abolished the stimulation, indicating anti-inflammatory activity of this extract. CONCLUSIONS: Thus various Echinacea extracts can inhibit the proliferation of these parasites and at least one can reverse the pro-inflammatory activity of Leishmania donovani.