Simultaneous quantitation of rosuvastatin and ezetimibe in human plasma by LC–MS/MS: Pharmacokinetic study of fixed‐dose formulation and separate tablets

A simple, high‐throughput and highly sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method has been developed for the simultaneous estimation of rosuvastatin and free ezetimibe. Liquid–liquid extraction was carried out using methyl‐tert butyl ether after prior acidification from 300 μL human plasma. The recovery for both the analytes and their deuterated internal standards (ISs) ranged from 95.7 to 99.8%. Rosuvastatin and ezetimibe were separated on Symmetry C₁₈ column using acetonitrile and ammonium formate buffer, pH 3.5 (30:70, v/v) as the mobile phase. The analytes were well resolved with a resolution factor of 3.8. Detection and quantitation were performed under multiple reaction monitoring using ESI(+) for rosuvastatin (m/z 482.0 → 258.1) and ESI(−) for ezetimibe (m/z 407.9 → 271.1). A linear response function was established in the concentration ranges of 0.05–50.0 ng/mL and 0.01–10.0 ng/mL for rosuvastatin and ezetimibe, respectively, with correlation coefficient, r² ≥ 0.9991. The IS‐normalized matrix factors for the analytes ranged from 0.963 to 1.023. The developed method was successfully used to compare the pharmacokinetics of a fixed‐dose combination tablet of rosuvastatin‐ezetimibe and co‐administered rosuvastatin and ezetimibe as separate tablets to 24 healthy subjects. The reliability of the assay was also assessed by reanalysis of 115 subject samples.     

Development and validation of a high‐throughput assay for the quantification of multiple green tea‐derived catechins in human plasma

A rapid, accurate and robust method for the determination of catechin (C), epicatechin (EC), gallocatechin (GC), epigallocatechin (EGC), catechin gallate (Cg), epicatechin gallate (ECg), gallocatechin gallate (GCg) and epigallocatechin gallate (EGCg) concentrations in human plasma has been developed. The method utilizes protein precipitation following enzyme hydrolysis, with chromatographic separation and detection using reversed‐phase liquid chromatography–tandem mass spectrometry (LC–MS/MS). Traditional issues such as lengthy chromatographic runtimes, sample and extract stability, and lack of suitable internal standards have been addressed. The method has been evaluated using a comprehensive validation procedure, confirming linearity over appropriate concentration ranges, and inter/intra‐batch precision and accuracies within suitable thresholds (precisions within 13.8% and accuracies within 12.4%). Recoveries of analytes were found to be consistent between different matrix samples, compensated for using suitable internal markers and within the performance of the instrumentation used. Similarly, chromatographic interferences have been corrected using the internal markers selected. Stability of all analytes in matrix is demonstrated over 32 days and throughout extraction conditions. This method is suitable for high‐throughput sample analysis studies.     

基于COLLATE融合多图谱的心脏电影MRI右心室分割

右心室分割对肺动脉高压等疾病的心功能分析具有重要的临床意义.然而,右心室心肌薄、易变且不规则,其传统的医学图像分割方法仍然未能取得突破性进展.本文提出基于COLLATE（Consensus Level,Labeler Accuracy and Truth Estimation）的多图谱分割方法,首先以归一化互信息为相似测度对目标图像和图谱集进行B样条配准以获取粗分割结果;然后利用COLLATE对粗分割结果进行融合;最后采用基于形状约束的区域生长算法修正出现错误的数据.10例临床心脏磁共振短轴电影图像被用于算法验证.本文还将使用基于COLLATE的多图谱分割方法得到的结果与深度学习算法及手动分割进行了比较.结果显示与深度学习算法比较,使用本文算法得到的射血分数（Ejection Fraction,EF）与手动分割更加一致和相关,表明该算法的分割结果有望辅助临床心脏功能诊断.     

两相同部件温贮备可修的人机系统解的性质分析

本文首先用强连续算子半群理论证明了两相同部件温贮备可修的人机系统动态非负解的存在唯一性 ,然后证明了 0是系统主算子的本征值 ,并得到 0本征值对应的本征向量是正的 ,从而系统存在稳态正解 .     

曲线拟合的广义最小一乘法

介绍了最小一乘法的方程式解法;讨论了这种方程式解法与最小一乘逼近之间的关系;说明了它不仅适用于线性函数类也适用于非线性函数类的最佳逼近的实现;提出了零偏差点附近数据变化的两个重要特征;建立了一种具有"人为"因素的广义最小一乘法;并给出了该法在预测方面的几个应用实例.     

左O-解析函数紧致奇点的可去性

借助于Adams等人的代数方法,我们证明了多八元数左O-解析函数以及满足一类微分方程的左O-解析函数的紧致奇点的可去性.     

Approximate Entropy of Brain Network in the Study of Hemispheric Differences

Human brain, a dynamic complex system, can be studied with different approaches, including linear and nonlinear ones. One of the nonlinear approaches widely used in electroencephalographic (EEG) analyses is the entropy, the measurement of disorder in a system. The present study investigates brain networks applying approximate entropy (ApEn) measure for assessing the hemispheric EEG differences; reproducibility and stability of ApEn data across separate recording sessions were evaluated. Twenty healthy adult volunteers were submitted to eyes-closed resting EEG recordings, for 80 recordings. Significant differences in the occipital region, with higher values of entropy in the left hemisphere than in the right one, show that the hemispheres become active with different intensities according to the performed function. Besides, the present methodology proved to be reproducible and stable, when carried out on relatively brief EEG epochs but also at a 1-week distance in a group of 36 subjects. Nonlinear approaches represent an interesting probe to study the dynamics of brain networks. ApEn technique might provide more insight into the pathophysiological processes underlying age-related brain disconnection as well as for monitoring the impact of pharmacological and rehabilitation treatments.     

二步幂零李群上—类左不变微分算子亚椭圆的充要条件

本文我们用幂零李群表示的方法,给出了二步幂零李群上一类左不变微分算子是亚椭圆的充要条件．     

The number of primes is finite

For a positive integer let and let . The number of primes of the form is finite, because if , then is divisible by . The heuristic argument is given by which there exists a prime such that for all large ; a computer check however shows that this prime has to be greater than . The conjecture that the numbers are squarefree is not true because .

     

右消去幺半群、左正则带和左正则型A幺半群

本文利用右消去幺半群,左正则带建立了真左正则型A幺半群．在证明了任一左正则型A幺半群均有P－覆盖后,给出P－覆盖的结构．