Home About us Contact
|
Home About us Contact | ||
|
|
||
Reference Standards (reference + standards)
Selected AbstractsAnalyses of second-generation ,legal highs' in the UK: Initial findingsDRUG TESTING AND ANALYSIS, Issue 8 2010Simon D. Brandt Abstract In the UK, mephedrone and other so-called ,legal high' derivatives have recently been classified as Class B, Schedule I under the Misuse of Drugs Act 1971. Since then, alternative products have been advertised on a number of websites. In order to obtain an immediate snapshot of the situation, 24 products were purchased online from 18 UK-based websites over a period of 6 weeks following the ban in April 2010. Qualitative analyses were carried out by gas chromatography ion trap mass spectrometry using electron- and chemical ionization modes, nuclear magnetic resonance spectroscopy, and comparison with reference standards. Overall, the purchased products consisted of single cathinones or cathinone mixtures including mephedrone, butylone, 4-methyl- N -ethylcathinone, flephedrone (4-fluoromethcathinone) and MDPV (3,4-methylenedioxypyrovalerone), respectively. Benzocaine, caffeine, lidocaine, and procaine were also detected. The emphasis was placed on ,Energy 1' (NRG-1), a product advertised as a legal replacement for mephedrone-type derivatives usually claiming to contain naphyrone (naphthylpyrovalerone, O-2482). It was found that 70% of NRG-1 and NRG-2 products appeared to contain a mixture of cathinones banned in April 2010 and rebranded as ,new' legal highs, rather than legal chemicals such as naphyrone as claimed by the retailers. Only one out of 13 NRG-1 samples appeared to show analytical data consistent with naphyrone. These findings also suggest that both consumers and online sellers (unlike manufacturers and wholesalers) are, most likely unknowingly, confronted with the risk of criminalization and potential harm. Copyright © 2010 John Wiley & Sons, Ltd. [source] Differentiation of structural isomers in a target drug database by LC/Q-TOFMS using fragmentation predictionDRUG TESTING AND ANALYSIS, Issue 6 2010Elli Tyrkkö Abstract Isomers cannot be differentiated from each other solely based on accurate mass measurement of the compound. A liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOFMS) method was used to systematically fragment a large group of different isomers. Two software programs were used to characterize in silico mass fragmentation of compounds in order to identify characteristic fragments. The software programs employed were ACD/MS Fragmenter (ACD Labs Toronto, Canada), which uses general fragmentation rules to generate fragments based on the structure of a compound, and SmartFormula3D (Bruker Daltonics), which assigns fragments from a mass spectra and calculates the molecular formulae for the ions using accurate mass data. From an in-house toxicology database of 874 drug substances, 48 isomer groups comprising 111 compounds, for which a reference standard was available, were found. The product ion spectra were processed with the two software programs and 1,3 fragments were identified for each compound. In 82% of the cases, the fragment could be identified with both software programs. Only 10 isomer pairs could not be differentiated from each other based on their fragments. These compounds were either diastereomers or position isomers undergoing identical fragmentation. Accurate mass data could be utilized with both software programs for structural elucidation of the fragments. Mean mass accuracy and isotopic pattern match values (SigmaFit; Bruker Daltonics Bremen, Germany) were 0.9 mDa and 24.6 mSigma, respectively. The study introduces a practical approach for preliminary compound identification in a large target database by LC/Q-TOFMS without necessarily possessing reference standards. Copyright © 2010 John Wiley & Sons, Ltd. [source] Searching for anthropogenic contaminants in human breast adipose tissues using gas chromatography-time-of-flight mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2009Félix Hernández Abstract The potential of gas chromatography-time-of-flight mass spectrometry (GC-TOF MS) for screening anthropogenic organic contaminants in human breast adipose tissues has been investigated. Initially a target screening was performed for a list of 125 compounds which included persistent halogen pollutants [organochlorine (OC) pesticides, polychlorinated biphenylss (PCBs), polybrominated diphenyl ethers (PBDEs)], polyaromatic hydrocarbons (PAHs), alkylphenols, and a notable number of pesticides from the different fungicide, herbicide and insecticide families. Searching for target pollutants was done by evaluating the presence of up to five representative ions for every analyte, all measured at accurate mass (20-mDa mass window). The experimental ion abundance ratios were then compared to those of reference standards for confirmation. Sample treatment consisted of an extraction with hexane and subsequent normal-phase (NP) High performance liquid chromatography (HPLC) or SPE cleanup. The fat-free LC fractions were then investigated by GC-TOF MS. Full-spectral acquisition and accurate mass data generated by GC-TOF MS also allowed the investigation of nontarget compounds using appropriate processing software to manage MS data. Identification was initially based on library fit using commercial nominal mass libraries. This was followed by comparing the experimental accurate masses of the most relevant ions with the theoretical exact masses with calculations made using the elemental composition calculator included in the software. The application of both target and nontarget approaches to around 40 real samples allowed the detection and confirmation of several target pollutants including p,p,-DDE, hexachlorobenzene (HCB), and some polychlorinated biphenyls (PCBs) and polyaromatic hydrocarbons (PAHs). Several nontarget compounds that could be considered anthropogenic pollutants were also detected. These included 3,5-di- tert -butyl-4-hydroxy-toluene (BHT) and its metabolite 3,5-di- tert -butyl-4-hydroxybenzaldehyde (BHT-CHO), dibenzylamine, N -butyl benzenesulfonamide (N -BBSA), some naphthalene-related compounds and several PCBs isomers not included in the target list. As some of the compounds detected are xenoestrogens, the methodology developed in this paper could be useful in human breast cancer research. Copyright © 2008 John Wiley & Sons, Ltd. [source] Hematology and blood biochemistry in infant baboons (Papio hamadryas)JOURNAL OF MEDICAL PRIMATOLOGY, Issue 3 2003L.M. Havill Abstract: Although published normative reference standards for hematologic and clinical chemistry measures are available for adult baboons, their applicability to infants has not been addressed. We analyzed these measures in 110 infant baboons (55 females and 55 males) from a large breeding colony at the Southwest Regional Primate Research Center in San Antonio, Texas. The sample consists of olive baboons and olive/yellow baboon hybrids, 1 week to 12 months of age. We produced cross-sectional reference values and examined the effects of age, sex, and subspecies on these variables. Hematology reference ranges for infant baboons are similar to, but wider than, those for adults. Reference ranges for blood biochemistry measures are generally more dissimilar to adults, indicating that for many variables, reference ranges for adult baboons are not adequate for infants. Although sex and subspecies differences are rare, age accounts for more than 10% of the variance in many of the variables. [source] Critical appraisal of the management of severe malnutrition: 1.JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 10 2006Epidemiology, treatment guidelines Abstract: Hospital case-fatality rates for severe malnutrition in the developing world remain high, particularly in Africa where they have not changed much over recent decades. In an effort to improve case management, WHO has developed treatment guidelines. The aim of this review is to critically appraise the evidence for the guidelines and review important recent advances in the management of severe malnutrition. We conclude that not only is the evidence base deficient, but also the external generalisability of even good-quality studies is seriously compromised by the great variability in clinical practice between regions and types of health facilities in the developing world, which is much greater than between developed countries. The diagnosis of severe wasting is complicated by the dramatic change in reference standards (from CDC/WHO 1978 to CDC 2000 in EpiNut) and also by difficulties in accurate measurement of length. Although following treatment guidelines has resulted in improved outcomes, there is evidence against the statement that case-fatality rates (particularly in African hospitals) can be reduced below 5% and that higher rates are proof of poor practice, because there is wide variation in severity of illness factors. The practice of prolonged hospital treatment of severe malnutrition until wasting and/or oedema has resolved is being replaced by shorter hospital stays combined with outpatient or community follow-up because of advances in dietary management outside of hospital. [source] Analytical aspects of pharmaceutical grade chondroitin sulfatesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2007Nicola Volpi Abstract Chondroitin sulfate is a very heterogeneous polysaccharide in terms of relative molecular mass, charge density, chemical properties, biological and pharmacological activities. It is actually recommended by EULAR as a symptomatic slow acting drug (SYSADOA) in Europe in the treatment of knee osteoarthritis based on meta-analysis of numerous clinical studies. Chondroitin sulfate is also utilized as a nutraceutical in dietary supplements mainly in the United States. On the other hand, chondroitin sulfate is derived from animal sources by extraction and purification processes. As a consequence, source material, manufacturing processes, the presence of contaminants, and many other factors contribute to the overall biological and pharmacological actions of these agents. The aim of this review is to evaluate new possible more specific analytical approaches to the determination of the origin and purity of chondroitin sulfate preparations for pharmaceutical application and in nutraceuticals, such as the evaluation of the molecular mass values, the constituent disaccharides, and the specific and sensitive agarose-gel electrophoresis technique. Furthermore, a critical evaluation is presented, together with a discussion of the limits of these analytical approaches. Finally, the necessity for reference standards having high specificity, purity and well-known physico-chemical properties useful for accurate and reproducible quantitative analyses will be discussed. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3168,3180, 2007 [source] Quantitative analysis of the major constituents of St John's wort with HPLC-ESI-MSJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2005Dhammitha H. Chandrasekera A method was developed to profile the major constituents of St John's wort extracts using highperformance liquid chromatography-electrospray mass spectrometry (HPLC-ESI-MS). The objective was to simultaneously separate, identify and quantify hyperforin, hypericin, pseudohypericin, rutin, hyperoside, isoquercetrin, quercitrin and chlorogenic acid using HPLC-MS. Quantification was performed using an external standardisation method with reference standards. The method consisted of two protocols: one for the analysis of flavonoids and glycosides and the other for the analysis of the more lipophilic hypericins and hyperforin. Both protocols used a reverse phase Luna phenyl hexyl column. The separation of the flavonoids and glycosides was achieved within 35 min and that of the hypericins and hyperforin within 9 min. The linear response range in ESI-MS was established for each compound and all had linear regression coefficient values greater than 0.97. Both protocols proved to be very specific for the constituents analysed. MS analysis showed no other signals within the analyte peaks. The method was robust and applicable to alcoholic tinctures, tablet/capsule extracts in various solvents and herb extracts. The method was applied to evaluate the phytopharmaceutical quality of St John's wort preparations available in the UK in order to test the method and investigate if they contain at least the main constituents and at what concentrations. [source] SELECTION OF AN ASTRINGENCY REFERENCE STANDARD FOR THE SENSORY EVALUATION OF BLACK TEAJOURNAL OF SENSORY STUDIES, Issue 2 2004ZUZANA DROBNA ABSTRACT Astringent and bitter sensations are characteristic sensory qualities of black tea. Three different classes of potential astringent reference standards (two concentrations each of alum and tannic acid and three fruit juices) were evaluated in this study. The perceived astringency, bitterness and sourness of each were profiled using computerized time-intensity and compared with the astringent intensity of a standardized brew of black tea. The differences in temporal profiles of potential reference standards across taste attributes were evident and intensity ratings were found to be dependent upon the stimulus and its concentration. Both concentrations of tannic acid were evaluated as the highest in perceived bitterness. For the juices, a strong sour taste was perceived in addition to astringency. It was concluded that the best reference standard for the astringency of black tea is a solution of 0.7 g/L alum as it is low in perceived bitterness and sourness. [source] MATCHING RESULTS OF TWO INDEPENDENT HIGHLY TRAINED SENSORY PANELS USING DIFFERENT DESCRIPTIVE ANALYSIS METHODS,JOURNAL OF SENSORY STUDIES, Issue 5 2002VARAPHA LOTONG ABSTRACT Two independent, highly trained panels separately conducted descriptive analysis of orange juices using different descriptive analysis methods and sets of samples. Lexicons were developed independently. One panel evaluated 23 orange juice products and identified and referenced 24 attributes. The other panel evaluated 17 products and identified 17 attributes for testing. Though not identical, the lexicons developed by both panels were similar overall. To compare the sensory space of the product category, Principal Component Analysis (PCA) and sensory maps were developed separately for each panel. The comparison showed that the underlying sample spaces obtained from both panels were comparable in many ways. Key flavor characteristics for the same types of orange juice products were described similarly by both panels. These data indicate that the process of using highly trained panels that define attributes and use reference standards for descriptive sensory analysis can give objective and comparable information for a product category across different panels. [source] Standardization of allergen products: 1.ALLERGY, Issue 7 2009Detailed characterization of GMP-produced recombinant Bet v 1.0101 as biological reference preparation Background:, Standardization of allergen extracts requires the availability of well-characterized recombinant allergens, which can be used as reference standards provided by the European regulatory authorities. The objective of this study was the detailed physicochemical and immunological characterization of rBet v 1.0101, which shall be used in a ring trial within the framework of the Biological Standardization Programme BSP090 of the European Directorate for Quality of Medicines and Healthcare. Methods:, Recombinant Bet v 1.0101 Y0487 was produced under good manufacturing practice conditions and analysed by an array of physicochemical and immunological methods for identity, quantity, homogeneity, folding and denaturation, aggregation state and stability in solution, as well as biological activity. Results:, Batch Y0487 was shown to contain monomeric and well-folded protein being identical with rBet v 1.0101, as determined by mass spectrometry. SDS-PAGE, isoelectric focusing, deamidation analysis and size-exclusion chromatography with light scattering revealed sample homogeneity of >99.9%. Upon storage at +4°C batch Y0487 retained the monomeric state up to 3 months. Protein quantification determined by amino acid analysis was found coinciding with half-maximal inhibition of serum IgE in ELISA. Biological activity of batch Y0487 was shown to be comparable to natural Bet v 1 by IgG and IgE immunoblotting, as well as basophil and T-cell activation. Conclusion:, Recombinant Bet v 1.0101 Y0487 was characterized extensively by physicochemical and immunological methods. It was shown highly stable, monomeric and immunologically equivalent to its natural counterpart. Thus, it represents an appropriate candidate reference standard for Bet v 1. [source] Sociodemographic determinants of growth among Malian adolescent femalesAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2010Timothy F. Leslie In Africa, research concerning the social determinants of poor nutritional status has typically focused on children under 5 years of age and has used defined categorical boundaries based on international reference standards. In this article, stunting and wasting of 1,157 Malian adolescent girls is measured through both categorical and continuous data. The focus on adolescent girls is significant because there is relatively little literature examining this group, and because adolescence marks the time when girls gain greater workload responsibilities, autonomy of food choices, and, as a result of the adolescent growth spurt, require the greatest amount of caloric intake respective to their weight since infancy. To differentiate stunting and wasting causes, a number of socioeconomic, geographic, and demographic factors are explored. The findings suggest that continuous data provides a basis for modeling stunting and wasting superior to utilizing international reference categories. Estimations show that decreasing age, the presence of servants, a greater number of wives in a compound, and residence in a large urban area correlate with improved nutritional status while wealthier families appear to correlate with greater stunting and wasting, and no correlation exists with estimated energy expenditure. Future studies should incorporate continuous data, and the need exists for greater analysis of social determinants of growth indicators among adolescent females. Further, these findings have significant implications in the development of nutrition intervention programs aimed at the vulnerable population in Mali, leading us to conclude that factors beyond socioeconomic indicators such as household structure and location should be more fully examined. Am. J. Hum. Biol., 2010. © 2009 Wiley-Liss, Inc. [source] Persistence of growth stunting in a Peruvian high altitude community, 1964,1999AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2010Ivan G. Pawson The growth of children living in Nuñoa, a Peruvian high-altitude community, was studied over a 35-year period using data collected in 1964 and 1999. There had been evidence of a secular trend in growth in the mid-1980s, but this was before a period of sociopolitical upheaval lasting until the late 1990s partly linked to the activities of the Shining Path group and the Peruvian government's response. Anthropometric data for 576 children examined in 1964,1966 were compared with data from 361 children examined in 1999. Data were converted to Z Scores using NCHS/WHO reference standards. Compared with the 1964 cohort, boys in 1999 had marginally greater height Z Scores, but among females, the trend was reversed. Stunting prevalence had decreased from 1964 levels, but still approached 60% in both sexes, among the highest rates recorded for a modern world population. The prevalence of low weight for height was less than expected, possibly because of the compensatory effect of enlarged chest diameter. This anatomical feature may represent the effect of chronic hypoxic stress, causing growth of the chest cavity at the expense of growth in height. In view of modest improvements during the late 1980s in this population, we believe that the relatively poor growth status of children a decade later may result from food disruption associated with later political instability. Compared with children in a nearby community, which benefits from the socioeconomic infrastructure associated with a large copper mine, Nuñoa children continue to fare relatively poorly. Am. J. Hum. Biol. 2010. © 2009 Wiley-Liss, Inc. [source] Characterization of protostane triterpenoids in Alisma orientalis by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 11 2010Xin Liu A reliable and sensitive ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method has been optimized and established for analysis of protostane triterpenoids in a commonly used traditional Chinese herbal medicine Alisma orientalis (Sam.) Juzep. The separation of crude extract of A. orientalis was achieved on a Waters ACQUITY HSS T3 column (100,mm,×,2.1,mm, 1.8,µm) eluting with 0.1% (v/v) formic acid/acetonitrile. A total of 20 protostane triterpenoids including 19 known compounds and a new one were well separated within 7,min. The collision-induced dissociation (CID) tandem mass spectrometric (MS/MS) fragmentation patterns of protostane triterpenoids was firstly reported in this study. The hydrogen rearrangement at the C-23-OH leads to dissociation of the bond between C-23 and C-24 in the protostane triterpenoid skeleton during the CID process. This dissociation was the characteristic CID fragmentation pathway of this class of triterpenoids, and was useful for further differentiation of some positional isomers which contain an acetyl unit on the C-23 or C-24 position. The identities of isolated compounds were identified by comparing their retention times and CID fragmentation behaviors with those of reference standards or tentatively assigned by matching the empirical molecular formulae with those reported in the literature. It is concluded that this newly established UPLC/Q-TOF-MS method is a powerful approach for structural elucidation of protostane triterpenoids isolated from A. orientalis. Copyright © 2010 John Wiley & Sons, Ltd. [source] Product ion mass spectra of amphetamine-type substances, designer analogues, and ketamine using ultra-performance liquid chromatography/tandem mass spectrometry,RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 15 2006Luigino G. Apollonio This paper describes the application of ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) technology to separate and identify amphetamine-type substances (amphetamine, methamphetamine), common and novel designer analogues (MDA, MDMA, PMA, 4-MTA, MBDB), and ketamine using Acquity UPLC/Micromass Quattro Micro API mass spectrometer instrumentation (Waters Corporation, USA). From injection of drug reference standards, it was demonstrated that these compounds can be identified by product ion mass spectra in less than 4,min total analysis time, indicating that the technological advancements associated with UPLC/MS/MS allow it to serve as a powerful analytical tool for high-throughput testing. In addition to demonstrating the separation and response of these drug compounds under the stated UPLC/MS/MS conditions, we believe the acquired product ion spectra will be a beneficial reference to laboratories interested in incorporating the use of this technology in the routine analysis of drugs of abuse. Copyright © 2006 John Wiley & Sons, Ltd. [source] Synthesis and Antimycobacterial Activity of Azetidine-, Quinazoline-, and Triazolo-thiadiazole-containing PyrazinesARCHIV DER PHARMAZIE, Issue 4 2010Chandrakant G. Bonde Abstract The re-emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug-resistant strains of Mycobacterium tuberculosis, emphasizes the need for the discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clinical management prompted us to synthesize a novel series of N -[2-(substituted aryl)-3-chloro-4-oxoazetidin-1-yl]-2-(pyrazin-2-yloxy)acetamide, 6-(substituted aryl)-3-[(pyrazin-2-yloxy)methyl][1,2,4]triazolo[3,4- b][1,3,4]thiadiazole, and N -[6-({2-[(pyrazin-2-yloxy)acetyl] hydrazino}sulfonyl)-2-methyl-4-oxo-1,4-dihydroquinazolin-3(2H)yl]-substituted aryl sulfonamides. The compounds were synthesized using the appropriate synthetic route. All synthesized compounds were assayed in vitro for antimycobacterial activity against the H37 Rv strain of Mycobacterium tuberculosis. The minimum inhibitory concentration (MIC) was determined for the test compounds as well as for the reference standards. The compound which exhibited good antimycobacterial activity contains the substituents fluorine and methoxy. These electron-withdrawing or -donating substituents amend the lipophilicity of the test compounds which, in turn, alter the permeability across the bacterial cell membrane. Compounds 28, 37, and 43 showed good antimycobacterial activity while compound 51 showed a promising antimycobacterial activity. [source] Intraspecific genome size variation and morphological differentiation of Ranunculus parnassifolius (Ranunculaceae), an Alpine,Pyrenean,Cantabrian polyploid groupBIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 2 2010EDUARDO CIRES The aim of this study was to assess genome size variation and multivariate morphometric analyses to ascertain cytotype distribution patterns and the morphological differentiation within the Ranunculus parnassifolius group in the Pyrenees and the Alps. Although divergences in nuclear DNA content among different species within a genus are widely acknowledged, intraspecific variation is still a somewhat controversial issue. Holoploid and monoploid genome sizes (C- and Cx-values) were determined using propidium iodide flow cytometry in 125 plants of R. parnassifolius s.l. distributed across four European countries. Three different DNA ploidy levels were revealed in the study area: diploid (2n , 2x, 57.14%), triploid (2n , 3x, 1.19%), and tetraploid (2n , 4x, 41.67%). The mean population 2C-values ranged from 8.15 pg in diploids to 14.80 pg in tetraploids, representing a ratio of 1 : 1.8. Marked intraspecific/interpopulation differences in nuclear DNA content were found. Diploid populations prevail in the Pyrenees, although tetraploid cytotypes were reported throughout the distribution area. In general, mixed-cytotype populations were not found. The Spearman correlation coefficient did not reveal significant correlations between genome size and altitude, longitude, or latitude. Morphometric analyses and cluster analyses based on genome size variation revealed the presence of three major groups, which exhibited a particular biogeographical pattern. A new cytotype, DNA triploid, was found for the first time. Tetraploid populations showed constant nuclear DNA levels, whereas diploid populations from the Pyrenees, in which introgressive hybridization is suggested as a presumable trigger for genome size variation, did not. Scenarios for the evolution of geographical parthenogenesis in R. parnassifolius s.l. are discussed. Finally, the different levels of effectiveness between plant and animal reference standards are analysed. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101, 251,271. [source] Liquid chromatography,mass spectrometry for analysis of a novel ,2 -adrenoceptor agonist trantinterol and its metabolites in beagle dog urineBIOMEDICAL CHROMATOGRAPHY, Issue 3 2010Yanjuan Wang Abstract A liquid chromatography,tandem mass spectrometry method was developed for the identification of metabolites of trantinterol, a novel ,2 -adrenoceptor agonist, in beagle dog urine. The separation of metabolites was performed on a reversed-phase C8 column using 0.1% formic acid in water and methanol (70 : 30, v/v) as the mobile phase. The structural information and elemental information of metabolites were acquired by an electrospray ionization tandem mass spectrometer and a quadrupole time-of-flight mass spectrometer, respectively. A total of 13 metabolites were detected and characterized on the basis of their tandem MS/MS fragmentation patterns. The accurate masses of nine metabolites were determined and two metabolites were further confirmed by comparing with reference standards. The metabolic pathways of trantinterol in beagle dog are proposed. Copyright © 2009 John Wiley & Sons, Ltd. [source] Comparative analysis on microbial and rat metabolism of ginsenoside Rb1 by high-performance liquid chromatography coupled with tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 7 2008Guangtong Chen Abstract Ginsenoside Rb1 is an active protopanaxadiol saponin from Panax species. In order to compare the similarities and differences of microbial and mammalian metabolisms of ginsenoside Rb1, the microbial transformation by Acremonium strictum and metabolism in rats were comparatively studied. Microbial transformation of ginsenoside Rb1 by Acremonium strictum AS 3.2058 resulted in the formation of eight metabolites. Ten metabolites (M1,M10) were detected from the in vivo study in rats and eight of them were identified as the same compounds as those obtained from microbial metabolism by liquid chromatography,tandem mass spectrometry analysis and comparison with reference standards obtained from microbial metabolism. Their structures were identified as ginsenoside Rd, gypenoside XVII, 20(S)-ginsenoside Rg3, 20(R)-ginsenoside Rg3, ginsenoside F2, compound K, 12, -hydroxydammar-3-one-20(S) -O-, -d- glucopyranoside, and 25-hydroxyl-(E)-20(22)-ene-ginsenoside Rg3, respectively. The structures of the additional two metabolites were tentatively characterized as 20(22),24-diene-ginsenoside Rg3 and 25-hydroxyginsenoside Rd by HPLC-MS/MS analysis. M7,M10 are the first four reported metabolites in vivo. The time course of rat metabolism of ginsenoside Rb1 was also investigated. Copyright © 2008 John Wiley & Sons, Ltd. [source] Analysis of chemical and metabolic components in traditional Chinese medicinal combined prescription containing Radix Salvia miltiorrhiza and Radix Panax notoginseng by LC-ESI-MS methodsBIOMEDICAL CHROMATOGRAPHY, Issue 8 2007Ying-Jie Wei Abstract High-performance liquid chromatography,electrospray ionization-mass spectrometry (LC-ESI-MS) methods were developed for the analysis of chemical and metabolic components in traditional Chinese medicinal combined prescription containing Radix Salvia miltiorrhiza and Radix Panax notoginseng (commonly known as Fufang Danshen prescription, FDP). The HPLC experiments used a reversed-phase Zorbax C18 column with the column temperature at 30°C and a binary mobile phase system consisting of aqueous formic acid (0.1%, v/v) and acetonitrile using a gradient elution at the flow rate of 1.0 mL/min. The ESI-MS was operated with a single-quadrupole mass spectrometer in both negative and positive ion modes. 36 major chromatographic peaks of FDP, including 14 saponins, 13 phenolic acids and nine diterpenoid quinones were characterized by their MS spectra and in comparison with some of the reference standards. In addition, after oral administration of extraction of FDP, the rat's plasma, urine and feces were also analyzed; 53 metabolic components including 30 original components and 23 transformative components of FDP were detected, and possible metabolic pathways of some components in FDP were given. The analysis of chemical and metabolic components in FDP by HPLC-MS methods could be a useful means of identifying the multi-components of FDP and to hint at their possible metabolic mechanism of action in the body. Copyright © 2007 John Wiley & Sons, Ltd. [source] Liquid chromatography,tandem mass spectrometry for the identification of l -tetrahydropalmatine metabolites in Penicillium janthinellum and ratsBIOMEDICAL CHROMATOGRAPHY, Issue 1 2006Li Li Abstract l-Tetrahydropalmatine (l-THP) is an active alkaloid from Stephania ainiaca Diels. In order to compare the similarities and differences of microbial and mammalian metabolisms of l-THP, the microbial transformation by Penicillium janthinellum and metabolism in rats were investigated. Biotransformation of l-THP by Penicillium janthinellum AS 3.510 resulted in the formation of three metabolites. Their structures were identified as l-corydalmine, l-corypalmine and 9- O -desmethyl-l-THP, respectively, by comprehensive nuclear magnetic resonance and mass spectrometry (MS) analysis. Six metabolites (M1,M6) were detected from the in vivo study in rats and three of which (l-corydalmine, l-corypalmine and 9- O -desmethyl-l-THP) were identified as the same compounds as those obtained from microbial metabolism by liquid chromatography,tandem mass spectrometry (LC-MS[sol ]MS) analysis and comparison with reference standards obtained from microbial metabolism. The structures of the additional three metabolites were tentatively deduced as 2- O -desmethyl-l-THP and two di- O -demethylated l-THP by LC-MS[sol ]MS analysis. Time courses of microbial and rat metabolisms of l-THP were also investigated. Copyright © 2005 John Wiley & Sons, Ltd. [source] Human cytochromes mediating gepirone biotransformation at low substrate concentrationsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2003David J. Greenblatt Abstract Biotransformation of gepirone to 1-(2-pyrimidinyl)-piperazine (1-PP) and 3'-OH-gepirone, as well as two other hydroxylated metabolites, was studied in vitro using a human liver microsomal preparation and heterologously expressed human CYP3A4 and CYP2D6. The focus was on a low range of gepirone concentrations (1000 nM and below). Liver microsomes formed 1-PP and 3'-OH-gepirone with similar reaction velocities. Two other hydroxylated metabolites (2-OH- and 5-OH-gepirone) were also formed, but pure reference standards were not available for purposes of quantitative analysis. The CYP3A inhibitor ketoconazole completely eliminated 1-PP formation, reduced 3'-OH-gepirone formation to less than 20% of control, and reduced 2-OH-gepirone formation to 7% of control. All metabolites were formed by expressed CYP3A4; however, CYP2D6 formed 3'-OH- and 5-OH-gepirone, but not 1-PP or 2-OH-gepirone. Based on estimated relative abundances of the two isoforms in human liver, CYP3A4 was predicted to account for more than 95% of net clearance of gepirone in vivo at low concentrations approaching the therapeutic range. CYP2D6 would account for less than 5% of net clearance. The findings are consistent with previous in vitro studies of gepirone using higher substrate concentrations. Copyright © 2003 John Wiley & Sons, Ltd. [source] Prevention of medication errors: detection and auditBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2009Germana Montesi 1. Medication errors have important implications for patient safety, and their identification is a main target in improving clinical practice errors, in order to prevent adverse events. 2. Error detection is the first crucial step. Approaches to this are likely to be different in research and routine care, and the most suitable must be chosen according to the setting. 3. The major methods for detecting medication errors and associated adverse drug-related events are chart review, computerized monitoring, administrative databases, and claims data, using direct observation, incident reporting, and patient monitoring. All of these methods have both advantages and limitations. 4. Reporting discloses medication errors, can trigger warnings, and encourages the diffusion of a culture of safe practice. Combining and comparing data from various and encourages the diffusion of a culture of safe practice sources increases the reliability of the system. 5. Error prevention can be planned by means of retroactive and proactive tools, such as audit and Failure Mode, Effect, and Criticality Analysis (FMECA). Audit is also an educational activity, which promotes high-quality care; it should be carried out regularly. In an audit cycle we can compare what is actually done against reference standards and put in place corrective actions to improve the performances of individuals and systems. 6. Patient safety must be the first aim in every setting, in order to build safer systems, learning from errors and reducing the human and fiscal costs. [source] Cerebral palsy and intrauterine growth in single births: European collaborative studyCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 2 2004Richard Reading Background Cerebral palsy seems to be more common in term babies whose birthweight is low for their gestational age at delivery, but past analyses have been hampered by small datasets and Z -score calculation methods. Methods We compared data from 10 European registers for 4503 singleton children with cerebral palsy born between 1976 and 1990 with the number of births in each study population. Weight and gestation of these children were compared with reference standards for the normal spread of gestation and weight-for-gestational age at birth. Findings Babies of 32,42 weeks' gestation with a birthweight for gestational age below the 10th percentile (using fetal growth standards) were 4,6 times more likely to have cerebral palsy than were children in a reference band between the 25th and 75th percentiles. In children with a weight above the 97th percentile, the increased risk was smaller (from 1.6 to 3.1), but still significant. Those with a birthweight about 1 SD above average always had the lowest risk of cerebral palsy. A similar pattern was seen in those with unilateral or bilateral spasticity, as in those with a dyskinetic or ataxic disability. In babies of less than 32 weeks' gestation, the relation between weight and risk was less clear. Interpretation The risk of cerebral palsy, like the risk of perinatal death, is lowest in babies who are of above average weight-for-gestation at birth, but risk rises when weight is well above normal as well as when it is well below normal. Whether deviant growth is the cause or a consequence of the disability remains to be determined. [source] | ||||||||||||||||