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排序方式: 共有507条查询结果,搜索用时 31 毫秒
51.
目的: 建立测定大鼠血浆中藤黄酸葡萄糖酯浓度的UPLC方法,并探讨其在大鼠体内的药代动力学。方法: 以新藤黄酸为内标,建立大鼠血浆中藤黄酸葡萄糖酯的UPLC测定方法。采用该方法测定大鼠单剂量静脉注射2、 4 、8 mg/kg 藤黄酸葡萄糖酯后,不同时间点大鼠血浆中的藤黄酸葡萄糖酯的浓度,对其血药浓度-时间采用DAS 2.1 软件拟合,计算药动学参数。结果: 血浆中藤黄酸葡萄糖酯在 0.05~14.0 mg/L 浓度范围内线性关系良好(r=0.9999) ,定量下限为 0.05 mg/L,提取回收率均大于87%,其日内日间RSD均小于10% ,藤黄酸葡萄糖酯按2、4和 8 mg/kg 静脉给药后,在大鼠体内的t1/2分别为(16.66±1.56)、(16.81±2.21) 和(17.88±2.05) min,AUC0-t 分别为(12.92±13.14)、(37.3±18.58) 和 (68.22±20.91) min·mg·L-1。结论: 所建立的UPLC方法操作简便、快速、专属性强,能满足藤黄酸葡萄糖酯在大鼠体内的药代动力学研究。 相似文献
52.
Wang J 《Mass spectrometry reviews》2009,28(1):50-92
Macrolides are a group of antibiotics that have been widely used in human medical and veterinary practices. Analysis of macrolides and related compounds in food, biological, and environmental matrices continue to be the focus of scientists for the reasons of food safety, pharmacokinetic studies, and environmental concerns. This article presents an overview on the primary biological properties of macrolides and their associated analytical issues, including extraction, liquid chromatography-mass spectrometry (LC-MS), method validation, and measurement uncertainty. The main techniques that have been used to extract macrolides from various matrices are solid-phase extraction and liquid-liquid extraction. Conventional liquid chromatography (LC) with C18 columns plays a dominant role for the determination of macrolides, whereas ultra-performance liquid chromatography (UPLC) along with sub-2 microm particle C18 columns reduces run time and improves sensitivity. Mass spectrometry (MS), serving as a universal detection technique, has replaced ultraviolet (UV), fluorometric, and electrochemical detection for multi-macrolide analysis. The triple-quadrupole (QqQ), quadrupole ion trap (QIT), triple-quadrupole linear ion trap, time-of-flight (TOF), and quadrupole time-of-flight (QqTOF) mass spectrometers are current choices for the determination of macrolides, including quantification, confirmation, identification of their degradation products or metabolites, and structural elucidation. LC or UPLC coupled to a triple-quadrupole mass spectrometer operated in the multiple-reaction monitoring (MRM) mode (LC/MS/MS) is the first choice for quantification. UPLC-TOF or UPLC-QqTOF has been recognized as an emerging technique for accurate mass measurement and unequivocal identification of macrolides and their related compounds. 相似文献
53.
Belloli C Lai OR Ormas P Zizzadoro C Sasso G Crescenzo G 《Journal of dairy science》2006,89(7):2465-2472
The pharmacokinetics and mammary excretion of imidocarb dipropionate, a therapeutic/prophylactic agent against a variety of tick-borne hemoparasitic diseases in domestic animals, have been investigated in sheep and goats. A commercial formulation of imidocarb di-propionate was injected i.m. at a single dose of 3 mg/kg of body weight in 7 mature lactating ewes and 8 lactating does in good health. Blood samples were collected for 48 h after administration and milk samples were collected every 12 h for 10 d. A weak cation-exchange solid-phase procedure was used to remove imidocarb from plasma. A hexane/isoamyl alcohol liquid-liquid procedure was adopted to extract the drug from the milk of sheep. The same method was used for goat milk after exposing the matrices to enzymatic digestion. The extracted samples were analyzed by HPLC. The i.m. disposition kinetics of imidocarb in the 2 species showed significant differences in the rate of elimination (0.0075 ± 0.002 and 0.025 ± 0.004 L/h in sheep and goats, respectively), being faster in ewes than in does. Nevertheless, a smaller area under the concentration-time curve (12.21 ± 0.76 and 9.49 ± 0.54 μg/mL per h in sheep and goats, respectively), a larger volume of distribution (4.18 ± 0.44 and 7.68 ± 0.57 L/kg in sheep and goats, respectively), and a longer mean residence time (9.07 ± 0.77 and 14.75 ± 2.20 h in sheep and goats, respectively) were found in goats, suggesting a more rapid and effective drug storage in tissues during the first 48 h after the injection. The concentrations of imidocarb in milk of both species were higher than in plasma. However, a fast passage through the blood-milk barrier and a high storage of imidocarb were observed in the milk of ewes, whereas the drug concentrations were not as high nor was the extent of drug penetration from blood to milk as great in the milk of goats (AUCmilk 0-48/AUCplasma 0-48 = 2.5 ± 0.45 and 1.26 ± 0.27 in sheep and goat, respectively). Despite the differences in pharmacokinetic behavior, and considering the sensitivity of pathogens to imidocarb, the same dosage regimen can be used for clinical efficacy against Babesia spp. infection in both species. In contrast, the differences in depletion of imidocarb residue in milk and the large variability in mammary drug elimination found in goats suggests that great care should be taken in defining the withdrawal time in small ruminant dairy species. 相似文献
54.
Liou JP Mahindroo N Chang CW Guo FM Lee SW Tan UK Yeh TK Kuo CC Chang YW Lu PH Tung YS Lin KT Chang JY Hsieh HP 《ChemMedChem》2006,1(10):1106-1118
The concise synthesis and structure-activity relationship (SAR) studies of 3-aroylindoles were carried out in an effort to improve the potency and solubility of anticancer drug candidate BPR0L075 (8) by exploring structure modifications through three regimens: substitution of the B ring, at the N1 position, and of the 3-carbonyl linker. The SAR information revealed that the methoxy group of the B ring could be replaced with an electron-donating group such as methyl (in compound 9) or N,N-dimethylamino (in compound 13) while retaining both strong cytotoxic and antitubulin activities. The introduction of amide (compounds 30-33) and carbamate (compounds 34-37) functionalities at the N1 position of 8 gave analogues with potent antiproliferative activities. The cytotoxic potency of 8 was improved by replacing the carbonyl group with sulfide (compound 41) or oxygen (compound 43), indicating that the carbonyl moiety is important but not essential. The N,N-dimethylamino derivative 13 not only displayed potent cytotoxicity and antitubulin activity, but also showed a markedly improved physicochemical profile relative to the parent compound. 相似文献
55.
基于药代动力学参数优化方法PKAIN人工免疫网络算法,提出了迭代分组并发单纯形算子,并实现了线性网络抑制函数以简化人工免疫网络的参数设置。为了加快算法的搜索速度和搜索精度,提出了新型的人工免疫网络单纯形混合算法(PKAIN_spx),用人工免疫网络实现粗粒度全局搜索,随后用单纯形进行精确搜索。仿真实验对改进的PKAIN算法(PKAIN_in)、人工免疫网络单纯形混合算法(PKAIN_spx)以及PKAIN算法进行了比较分析,结果表明PKAIN_spx算法在药代动力学参数优化中取得良好的实验效果。 相似文献
56.
57.
本研究建立了液相色谱-串联质谱(LC-MS/MS)法测定比格犬血浆中丁酸氯维地平浓度,用来研究自制的丁酸氯地平脂肪乳注射液与原研产品在比格犬体内的药代动力学参数,同时比较其生物等效性。实验以氨氯地平为内标,选取Phenomenex Luna C8色谱柱(2.0 mm×150 mm×5 μm),以甲醇0.1%甲酸溶液(82∶18,V/V)为流动相,采用Waters Quattro Micro API的正离子检测方式,用MassLynx4.1软件进行数据处理。结果表明,丁酸氯维地平标准曲线的线性范围为0.4~100 μg/L。主要的药代动力学参数:参比制剂和试验制剂的Cmax平均值分别为(58.748±16.738)μg/L和(53.706±18.963)μg/L;Tmax分别为(2.938±0.678)μg/L和(2.875±0.991)μg/L;T1/2分别为(11.88±3.824)min和(11.587±3.634)min;AUC0→t分别为(1 883.821±647.882)μg•min/L和(1 856.541±590.653) μg•min/L;AUC0→∞分别为(1 889.834±649.135) μg•min/L和(1 863.485±592.039) μg•min/L。方差分析表明,这两种制剂的主要药动学参数之间无明显差异;双单侧t检验结果表明,两制剂在比格犬体内为生物等效制剂。 相似文献
58.
《Drug development and industrial pharmacy》2013,39(11):1340-1347
Purpose: In this study, a thermosensitive in situ gelling vehicle was prepared to increase the precorneal resident time and the bioavailability of methazolamide (MTA). Method: Poloxamer analogs were used as the gelling agents, and the in situ gel was obtained by using a cold method. The gelation temperature, rheological properties, in vitro release as well as in vivo evaluation (the elimination of MTA in aqueous humor and intraocular-lowering effect) of the optimized formulations were investigated. Results: The optimum concentrations of poloxamer analogs for the in situ gel-forming delivery system were 21% (w/w) poloxamer 407 and 10% (w/w) poloxamer P188. This formulation was able to flow freely under nonphysiological conditions and underwent sol–gel transition in the cul-de-sac upon placement into the eye. In vitro release studies demonstrated a diffusion-controlled release of MTA from the poloxamer solutions over a period of 10 hours. In vivo evaluation indicated that the poloxamer solutions had a better ability to retain drug than MTA eyedrops did. Conclusion: These results suggested that in situ gelling ophthalmic drug delivery system may hold some promise in ocular MTA delivery. 相似文献
59.
Kristin Yaehne Amy Tekrony Aisling Clancy Yiota Gregoriou John Walker Kwin Dean Trinh Nguyen Amber Doiron Kristina Rinker Xiao Yu Jiang Sarah Childs David Cramb 《Small (Weinheim an der Bergstrasse, Germany)》2013,9(18):3118-3127
Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined. It is shown that deposition is dependent on surface charge. Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry. These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size. 相似文献
60.
Comparison of pharmacokinetics in beagle dogs of nimesulide bilayer tablets with dispersible tablets
《Drug development and industrial pharmacy》2013,39(1):156-161
The purpose of this study was to compare the in vitro release and the in vivo pharmacokinetics of bilayer tablets with the conventional dispersible tablets of nimesulide. The tablets were administered to beagle dogs and the plasma levels of nimesulide were determined by high-performance liquid chromatography-MS/MS. The pharmacokinetic parameters were calculated using a noncompartmental model. The bilayer tablets showed a biphasic in vitro release pattern with initial burst release and sustained release following the quasi-Fickian diffusion-based release mechanism. The Cmax, tmax, mean residence time (MRT), and area under the curve from 0 to 36 h were 10.8 ± 4.2 μg/mL, 2.3 ± 1.0 h, 6.7 ± 2.1 h, 81.5 ± 26.7 μg·h/mL for the bilayer tablets and 14.8 ± 5.8 μg/mL, 2.7 ± 0.8 h, 5.6 ± 0.9 h, 95.4 ± 44.2 μg·h/mL for the dispersible tablets. Compared with the dispersible tablets, the bilayer tablets have lower Cmax, similar tmax, and longer MRT. The aforementioned pharmacokinetic parameters, especially the MRT demonstrated to be valuable for evaluating the biphasic characteristics. This study provides a promising in vivo evaluation method for the bilayer tablets with biphasic release pattern. 相似文献