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51.
Alan M. Goldberg John M. Frazier David Brusick Michael S. Dickens Oliver Flint Stephen D. Gettings Richard N. Hill Robert L. Lipnick Kevin J. Renskers June A. Bradlaw Robert A. Scala Bellina Veronesi Sidney Green Neil L. Wilcox Rodger D. Curren 《In vitro cellular & developmental biology. Animal》1993,29(9):688-692
Summary The development and application of in vitro alternatives designed to reduce or replace the use of animals, or to lessen the
distress and discomfort of laboratory animals, is a rapidly developing trend in toxicology. However, at present there is no
formal administrative process to organize, coordinate, or evaluate validation activities. A framework capable of fostering
the validation of new methods is essential for the effective transfer of new technologic developments from the research laboratory
into practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks,
a data bank, and reference laboratories. The creation of a Scientific Advisory Board composed of experts in the various aspects
and endpoints of toxicity testing, and representing the academic, industrial, and regulatory communities, is recommended.
Test validation acceptance is contingent on broad buy-in by disparate groups in the scientific community—academics, industry,
and government. This is best achieved by early and frequent communication among parties and agreement on common goals. It
is hoped that the creation of a validation infrastructure composed of the elements described in this report will facilitate
scientific acceptance and utilization of alternative methodologies and speed implementation of replacement, reduction, and
refinement alternatives in toxicity testing. 相似文献
52.
Activity-based protein profiling (ABPP) is recognized as a powerful and versatile chemoproteomic technology in drug discovery. Central to ABPP is the use of activity-based probes to report the activity of specific enzymes or reactivity of amino acid types in complex biological systems. Over the last two decades, ABPP has facilitated the identification of new drug targets and discovery of lead compounds in human and infectious disease. Furthermore, as part of a sustained global effort to illuminate the druggable proteome, the repertoire of target classes addressable with activity-based probes has vastly expanded in recent years. Here, we provide an overview of ABPP and summarise the major technological advances with an emphasis on probe development. 相似文献
53.
Estimation of Enantiomeric Impurity in Piperidin‐3‐Amine by Chiral HPLC With Precolumn Derivatization 下载免费PDF全文
Chittabathina Venkata Raghunadha Babu Nagi Reddy Vuyyuru K. Padmaja Reddy M.V. Suryanarayana K. Mukkanti 《Chirality》2014,26(12):775-779
A simple, precise, accurate, robust chiral high‐performance liquid chromatographic (chiral HPLC) method was developed for estimation of (S)‐piperidin‐3‐amine (S‐isomer) in (R)‐piperidin‐3‐amine dihydrochloride (R‐AMP). As AMP is a high‐melting solid and nonchromophoric compound, development of a suitable chiral method is a challenging task. The proposed chiral HPLC‐UV method involves a precolumn derivatization technique with para toluene sulphonyl chloride (PTSC) in the presence of a base to introduce chromophore into analytes. It utilizes chiralpak AD‐H column with a simple mobile phase of 0.1% diethyl amine in ethanol with a 0.5 mL/min flow rate. Analytes were monitored by using a UV detector at 228 nm. The resolution between the two enantiomers was more than 4.0. The developed method was validated as per current International Conference on Harmonization (ICH) guidelines. Chirality 26:775–779, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
54.
Otolith growth and age estimation in the European hake 总被引:5,自引:0,他引:5
The internal sulcal rings in Merluccius merluccius otoliths cannot be considered as annuli. In the absence of a strong seasonal Zeitgeber, hake otoliths in the Mediterranean did not lay down an interpretable ring pattern that would be useful for age determination. A total of 484 sagittal otoliths from specimens ranging between 6 and 94 cm L T was studied in monthly samples from the Gulf of Lions in 1989–1990. Transverse, burnt otolith sections was analysed with an image analysis system using enhanced and filtered images and using a fast Fourier transform (FFT) function to avoid subjectivity in ring interpretation. The otolith radius-fish length relationship showed allometric growth and sexual dimorphism. The ring pattern was consistent for the sulcal rings in both sexes. Changes in the marginal increment showed the formation of multiple sulcal rings, of both environmental and physiological origin. The ring pattern depended on the sex and sexual activity. 相似文献
55.
三种转基因酵母法筛选类雌激素活性物质方法的比较 总被引:1,自引:0,他引:1
利用转基因酵母菌株,分别采用摇瓶法、96孔板法和单板法筛选类雌激素活性化学品,并对实验参数进行了优化。通过对工作光密度及β半乳糖苷酶反应时间的优化,使改进后的转基因酵母筛选法筛选一批样品的时间从原来需要的几天缩短为半天。并且在时间缩短的同时,仍保留原来检测的高灵敏度和准确性,也节省了大量的试验耗材,达到了能应用于环境样品中类雌激素活性物质的快速测定的目的。
相似文献
56.
The potential of viral contamination is a regulatory concern for continuous cell line-derived pharmaceutical proteins. Complementary and redundant safety steps, including an evaluation of the viral clearance capacity of unit operations in the purification process, are performed prior to registration and marketing of biotechnology pharmaceuticals. Because process refinement is frequently beneficial, CBER/FDA has published guidance facilitating process improvement by delineating specific instances where the bracketing and generic approaches are appropriate for virus removal validation. In this study, a generic/matrix study was performed using Q-Sepharose Fast Flow (QSFF) chromatography to determine if bracketing and generic validation can be applied to anion exchange chromatography. Key operational parameters were varied to upper and lower extreme values and the impact on viral clearance was assessed using simian virus 40 (SV40) as the model virus. Operational ranges for key chromatography parameters were identified where an SV40 log(10) reduction value (LRV) of >or=4.7 log(10) is consistently achieved. On the basis of the apparent robustness of SV40 removal by Q-anion exchange chromatography, we propose that the concept of "bracketed generic" validation can be applied to this and potentially other chromatography unit operations. 相似文献
57.
Validated spectrofluorimetric method for the determination of tamsulosin in spiked human urine,pure and pharmaceutical preparations 下载免费PDF全文
A novel, sensitive and selective spectrofluorimetric method was developed for the determination of tamsulosin in spiked human urine and pharmaceutical preparations. The proposed method is based on the reaction of tamsulosin with 1‐dimethylaminonaphthalene‐5‐sulfonyl chloride in carbonate buffer pH 10.5 to yield a highly fluorescent derivative. The described method was validated and the analytical parameters of linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, recovery and robustness were evaluated. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over the range 1.22 × 10‐7 to 7.35 × 10‐6 M. LOD and LOQ were calculated as 1.07 × 10‐7 and 3.23 × 10‐7 M, respectively. The proposed method was successfully applied for the determination of tamsulosin in pharmaceutical preparations and the obtained results were in good agreement with those obtained using the reference method. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
58.
Development and validation of a sensitive spectrofluorimetric method for the determination of amoxapine in human plasma and urine 下载免费PDF全文
A selective and sensitive spectrofluorimetric method was developed and validated for the determination of amoxapine in human plasma and urine. The developed method is based on labeling with 5‐dimethylaminonaphthalene‐1‐sulfonyl chloride (dansyl chloride) and monitoring at 397 nm (excitation)/514 nm (emission). The method was validated for linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, recovery and robustness. The calibration curves were linear over a concentration range of 250–2500 and 50–1250 ng/mL for plasma and urine, respectively. The LOD values were calculated to be 13.31 and 13.17 ng/mL for plasma and urine, respectively. The proposed method was applied to study of amoxapine in human plasma and urine. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
59.
Biological characteristics of three co‐occurring species of armorhead from different genera vary markedly from previous results for the Pentacerotidae 下载免费PDF全文
Biological characteristics of Pentaceropsis recurvirostris, Paristiopterus gallipavo and Parazanclistius hutchinsi were determined from commercial gillnet samples from temperate south‐western Australian coastal waters. Growth zones in otoliths, with more than a few such zones, were readily detectable only after the otoliths had been sectioned. Visual analyses and modelling of the trends in marginal increments on sectioned otoliths demonstrate that these opaque zones are formed annually. Maximum ages of 55, 36 and 49 years, derived for P. recurvirostris, P. gallipavo and P. hutchinsi, respectively, reflect relatively low mortalities. These longevities greatly exceed those estimated, using otoliths, for Pentaceros wheeleri and Pentaceros richardsoni, which belong to the other pentacerotid subfamily. These differences may be due to the counts of ‘daily’ growth zones in sectioned otoliths of P. wheeleri not representing the complete age range of that species and the zones detected in whole otoliths of P. richardsoni not constituting the complete range of annually‐formed zones. Pentaceropsis recurvirostris, P. gallipavo and P. hutchinsi recruited into the fishery in the sampling area as 2–3 year‐old fishes. Pentaceropsis recurvirostris and P. hutchinsi exhibited little or no subsequent growth throughout the remainder of their protracted life, whereas, P. gallipavo continued to grow for c. 5 years and then underwent little further growth. Spawning of P. recurvirostris and P. hutchinsi peaked in the austral winter and autumn, respectively, but in the austral spring and summer with P. gallipavo, which is more typical of temperate species. Although the females of P. gallipavo and P. hutchinsi were mature, this did not apply to a few P. recurvirostris, some of which were >20 years old, implying that any given female of this species does not always spawn every year. Ovarian mass greatly exceeded testis mass, indicative of pair spawning, which is consistent with field observations. In contrast to P. recurvirostris and P. hutchinsi, the sex ratio was heavily biased towards males and the spawning period longer in P. gallipavo, suggesting that selection pressures for spawning success were greater for this latter species. 相似文献
60.
Chiral Separation of Uncharged Pomalidomide Enantiomers Using Carboxymethyl‐β‐Cyclodextrin: A Validated Capillary Electrophoretic Method 下载免费PDF全文
The racemic mixture of pomalidomide (POM), a second‐generation immunomodulatory uncharged drug, was separated into enantiomers by capillary zone electrophoresis for the first time. Seven different chargeable cyclodextrin (CD) derivatives were screened as complexing agents and chiral selectors, investigating the stability of the POM‐CD inclusion complexes and their enantiodiscriminating capacities. Based on preliminary experiments, carboxymethyl‐β‐CD (CM‐β‐CD) was found to be the most effective chiral selector. Factors influencing enantioseparation were systematically optimized, using an orthogonal experimental design. Optimal parameters (background electrolyte [BGE]: 50 mM Tris‐acetate buffer, pH 6.5, containing 15 mM CM‐β‐CD; capillary temperature: 20°C; voltage applied +15 kV) allowed baseline separation of POM enantiomers with a resolution as high as 4.87. The developed method was validated, in terms of sensitivity (limit of detection and limit of quantification), linearity, accuracy, repeatability, and intermediate precision. Chirality 28:199–203, 2016. © 2015 Wiley Periodicals, Inc. 相似文献