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排序方式: 共有144条查询结果,搜索用时 15 毫秒
1.
Veenu Bala Yashpal S. Chhonker Richard L. Sleightholm Ayrianne J. Crawford Michael A. Hollingsworth Daryl J. Murry 《Biomedical chromatography : BMC》2020,34(8):e4859
A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (MS/MS) method was developed and validated for the quantitation of the novel CDK5 inhibitor ‘20–223' in mouse plasma. Separation of analytes was achieved by a reverse-phase ACE Excel C18 column (1.7 μm, 100 × 2.1 mm) with gradient elution using 0.1% formic acid (FA) in methanol and 0.1% FA as the mobile phase. Analytes were monitored by MS/MS with an electrospray ionization source in the positive multiple reaction monitoring mode. The MS/MS response was linear over the concentration range 0.2–500 ng/mL for 20–223. The within- and between-batch precision were within the acceptable limits as per Food and Drug Administration guidelines. The validated method was successfully applied to plasma protein binding and in vitro metabolism studies. Compound 20–223 was highly bound to mouse plasma proteins (>98% bound). Utilizing mouse S9 fractions, in vitro intrinsic clearance (CLint) was 24.68 ± 0.99 μL/min/mg protein. A total of 12 phase I and II metabolites were identified with hydroxylation found to be the major metabolic pathway. The validate method required a low sample volume, was linear from 0.2 to 500 ng/mL, and had acceptable accuracy and precision. 相似文献
2.
Joshua Silva Eileen Carry Chen Xue Jifeng Zhang Jing Liang Jacques Y. Roberge Daryl L. Davies 《Molecules (Basel, Switzerland)》2021,26(6)
Alcohol use disorder (AUD) affects over 18 million people in the US. Unfortunately, pharmacotherapies available for AUD have limited clinical success and are under prescribed. Previously, we established that avermectin compounds (ivermectin [IVM] and moxidectin) reduce alcohol (ethanol/EtOH) consumption in mice, but these effects are limited by P-glycoprotein (Pgp/ABCB1) efflux. The current study tested the hypothesis that dihydromyricetin (DHM), a natural product suggested to inhibit Pgp, will enhance IVM potency as measured by changes in EtOH consumption. Using a within-subjects study design and two-bottle choice study, we tested the combination of DHM (10 mg/kg; i.p.) and IVM (0.5–2.5 mg/kg; i.p.) on EtOH intake and preference in male and female C57BL/6J mice. We also conducted molecular modeling studies of DHM with the nucleotide-binding domain of human Pgp that identified key binding residues associated with Pgp inhibition. We found that DHM increased the potency of IVM in reducing EtOH consumption, resulting in significant effects at the 1.0 mg/kg dose. This combination supports our hypothesis that inhibiting Pgp improves the potency of IVM in reducing EtOH consumption. Collectively, we demonstrate the feasibility of this novel combinatorial approach in reducing EtOH consumption and illustrate the utility of DHM in a novel combinatorial approach. 相似文献
3.
Yashpal S. Chhonker Richard L. Sleightholm Daryl J. Murry 《Biomedical chromatography : BMC》2019,33(2)
Moxidectin (MOX) has recently been approved by the US Food and Drug Administration for the treatment of river blindness in select populations. It is also being evaluated as an alternative for the use of ivermectin, widespread resistance to which is becoming a global health issue. Moreover, MOX is becoming increasingly used as a prophylactic antiparasitic in the cattle industry. In this study, we developed and validated an LC–MS/MS method of MOX in human, monkey and mouse plasma. The separation was achieved on an ACE C18 (50 × 3.0 mm, 3 μm) column with isocratic elution using 0.1% acetic acid and methanol–acetonitrile (1:1, v/v) as mobile phase. MOX was quantitated using MS/MS with an electrospray ionization source operating in negative multiple reaction monitoring mode. The multiple reaction monitoring precursor ion → product ion transitions for MOX and abamectin (IS) were m/z 638.40 → 236.30 and m/z 871.50 → 565.35 respectively. The MS/MS response was linear over the concentration range 0.1–1000 ng/mL in plasma with a correlation coefficient (r2) of 0.997 or better. The within‐ and between‐day precision (relative standard deviation, RSD) and accuracy were within the acceptable limits per US Food and Drug Administration guidelines. The method was successfully applied to an in vitro metabolic stability study of MOX. 相似文献
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Daryl Tingley 《Applicable analysis》2013,92(1-3):1-4
D. P. Mil'man and V. D. Mil'man considered sequences of decreasing nonempty closed bounded convex sets with empty intersection to obtain characteristics of non-reflexivity. They showed that in every nonreflexive space there is such a sequence which is ω-separated. We show that in every nonreflexive space there is also always such a sequence which is not ω-separated 相似文献
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Prof. Timothy J. Donohoe Adam R. Lacy Akshat H. Rathi Dr. Daryl S. Walter 《化学:亚洲杂志》2011,6(12):3214-3222
A new strategy that employs an exocyclic stereocenter to effect diastereocontrol in the tethered aminohydroxylation (TA) reaction is applied to the stereoselective synthesis of a range of amino alcohols in good to excellent yields, and with anti selectivities of up to 20:1. The influence of the reaction conditions and substrate parameters on the level of diastereocontrol is described. Furthermore, an “inside alkoxy” model is employed to rationalize the sense and degree of stereoselectivity observed in these systems. 相似文献
9.
Daryl Geller Domenico Marinucci 《Journal of Mathematical Analysis and Applications》2011,375(2):610-630
The construction of needlet-type wavelets on sections of the spin line bundles over the sphere has been recently addressed in Geller and Marinucci (2008) [14], and Geller et al. (2008, 2009) [12] and [13]. Here we focus on an alternative proposal for needlets on this spin line bundle, in which needlet coefficients arise from the usual, rather than the spin, spherical harmonics, as in the previous constructions. We label this system mixed needlets and investigate in full their properties, including localization, the exact tight frame characterization, reconstruction formula, decomposition of functional spaces, and asymptotic uncorrelation in the stochastic case. We outline astrophysical applications. 相似文献
10.
The first preparation of title compound 1 is accomplished. Its heterocyclic structure was characterized spectroscopically and by X‐ray structure analysis. 相似文献