Analytical method development and validation of anticancer agent, 5-fluorouracil,and its metabolites in biological matrices: An updated review

Abstract

5-fluorouracil (5-FU) refers to a fluorinated pyrimidine analogue that has been widely used as an anticancer agent for colon, head, and neck cancers. Detection of 5-FU and its metabolites; 5-fluorouridine and 5-fluoro-2-deoxyuridine in biological samples allows optimization of pharmacotherapy and encourages fundamental investigations of this medication. The development of accurate and reliable sample preparation, as well as analytical methods, is critical to isolate targeted analytes from complex matrices, apart from increasing detection sensitivity of analytes. With that, this paper presents a review of prior studies pertaining to chromatographic and electrophoretic methods that focused on the analysis of 5-FU and its metabolites in biological matrices such as plasma and urine. This paper concentrates on HPLC, GC and CE systems, which are the most commonly used strategies for analytical separation of 5-FU and its metabolites from samples. Detection of these antineoplastic agents at trace level demands highly sensitive and selective analytical methodologies. Application of these analytical techniques to biological matrices is reviewed with a focus on method development strategies, including types of mobile phases and background electrolytes employed in LC and CE systems.     

Theoretical investigation on submicron particle penetration through circular tubes inside a porous medium

The analytical infinite series solution of submicron particle transport in a circular tube bounded by a porous wall, such as a pinhole, is determined under the slip velocity boundary condition, and the solution is verified by using the experimental data in the previous studies for the specific cases. The results show that particle penetration rate increases with the increase of the porous parameter, the axial pressure drop, and the pinhole radius, whereas it decreases with increasing the pinhole length. The penetration rate of nano-particles are more sensitive to the variation of these parameters. However, the differences between the penetrations of particles ranging from 0.3 μm to 1 μm are not evident because the diffusion becomes weak gradually in this size range. In addition, a further comparison is performed between the analytical solution and the existing studies, and approximate expressions are presented for accurate calculation of particle penetration rate through pinholes appearing in porous materials including filter devices and masks.     

C_2^+ (X^4 Σ_g^-,1^4 Σ_u^+)离子体系解析势能函数、光谱常数和振动能级研究

采用多参考组态相互作用(MRCI)方法,结合aug-cc-pV6Z(AV6Z)基组,计算了C₂⁺(X⁴Σ_g^-,1⁴Σ_u⁺)的势能曲线,计算过程中考虑了Davidson修正和相对论效应,并将结果外推至完备基组(CBS)的极限.基于得到的单点能量,用最小二乘法方法进行了Murrell-Sorbie函数拟合,得到了势能函数解析式(APEF).基于APEF,计算了C₂⁺(X⁴Σ_g^-,1⁴Σ_u⁺)离子体系的离解能D_e,平衡核间距R_e,光谱常数ω_e,ω_eχ_e,B_e,α_e,结果与实验和其他理论计算值符合...     

级联掺磷光纤喇曼激光器的解析优化

讨论了二级级联喇曼光纤激光器的解析解和优化设计.通过引入几何平均功率、增益因子和归一化光纤有效长度,将描述泵浦光和斯托克斯光沿喇曼增益光纤分布的微分方程组简化成代数方程组,在对泵浦光采用线性传播近似后,获得了二级级联喇曼激光器的解析解.所获得的解析解同数值模拟结果吻合得很好.利用该解析解可方便和快速地讨论级联喇曼激光器的优化设计,计算不同泵浦功率下的最佳光纤长度、输出光纤光栅反射率和转换效率.泵谱功率越大,最佳光纤长度越短,最佳输出光纤光栅反射率越小.     

Flexible Implementation of the Trilinearity Constraint in Multivariate Curve Resolution Alternating Least Squares (MCR-ALS) of Chromatographic and Other Type of Data

Multivariate Curve Resolution Alternating Least Squares (MCR-ALS) can analyze three-way data under the assumption of a trilinear model using the trilinearity constraint. However, the rigid application of this constraint can produce unrealistic solutions in practice due to the inadequacy of the analyzed data to the characteristics and requirements of the trilinear model. Different methods for the relaxation of the trilinear model data requirements have been proposed, like in the PARAFAC2 and in the direct non-trilinear decomposition (DNTD) methods. In this work, the trilinearity constraint of MCR-ALS is adapted to different data scenarios where the profiles of all or some of the components of the system are shifted (not equally synchronized) or even change their shape among different slices in one of their data modes. This adaptation is especially useful in gas and liquid chromatography (GC and LC) and in Flow Injection Analysis (FIA) with multivariate spectroscopic detection. In a first data example, a synthetic LC-DAD dataset is built to investigate the possibilities of the proposed method to handle systematic changes (shifts) in the retention times of the elution profiles and the results are compared with those obtained using alternative methods like ATLD, PARAFAC, PARAFAC2 and DNTD. In a second data example, multiple wine samples were simultaneously analyzed by GC-MS where elution profiles presented large deviations (shifts) in their peak retention times, although they still preserve the same peak shape. Different modelling scenarios are tested and the results are also compared. Finally, in the third example, sample mixtures of acid compounds were analyzed by FIA under a pH gradient and monitored by UV spectroscopy and also examined by different chemometric methods using a different number of components. In this case, however, the departure of the trilinear model comes from the acid base speciation of the system depending on the pH more than from the shifting of the FIA diffusion profiles.     

Elemental Chemometrics as Tools to Depict Stalked Barnacle (Pollicipes pollicipes) Harvest Locations and Food Safety

The stalked barnacle Pollicipes pollicipes is an abundant species on the very exposed rocky shore habitats of the Spanish and Portuguese coasts, constituting also an important economical resource, as a seafood item with high commercial value. Twenty-four elements were measured by untargeted total reflection X-ray fluorescence spectroscopy (TXRF) in the edible peduncle of stalked barnacles sampled in six sites along the Portuguese western coast, comprising a total of 90 individuals. The elemental profile of 90 individuals originated from several geographical sites (N = 15 per site), were analysed using several chemometric multivariate approaches (variable in importance partial least square discriminant analysis (VIP-PLS-DA), stepwise linear discriminant analysis (S-LDA), linear discriminant analysis (LDA), random forests (RF) and canonical analysis of principal components (CAP)), to evaluate the ability of each approach to trace the geographical origin of the animals collected. As a suspension feeder, this species introduces a high degree of background noise, leading to a comparatively lower classification of the chemometric approaches based on the complete elemental profile of the peduncle (canonical analysis of principal components and linear discriminant analysis). The application of variable selection approaches such as the VIP-PLS-DA and S-LDA significantly increased the classification accuracy (77.8% and 84.4%, respectively) of the samples according to their harvesting area, while reducing the number of elements needed for this classification, and thus the background noise. Moreover, the selected elements are similar to those selected by other random and non-random approaches, reinforcing the reliability of this selection. This untargeted analytical procedure also allowed to depict the degree of risk, in terms of human consumption of these animals, highlighting the geographical areas where these delicacies presented lower values for critical elements compared to the standard thresholds for human consumption.     

Chemometric Tools to Point Out Benchmarks and Chromophores in Pigments through Spectroscopic Data Analyses

Spectral preprocessing data and chemometric tools are analytical methods widely applied in several scientific contexts i.e., in archaeometric applications. A systematic classification of natural powdered pigments of organic and inorganic nature through Principal Component Analysis with a multi-instruments spectroscopic study is presented here. The methodology allows the access to elementary and molecular unique benchmarks to guide and speed up the identification of an unknown pigment and its recipe. This study is conducted on a set of 48 powdered pigments and tested on a real-case sample from the wall painting in S. Maria Delle Palate di Tusa (Messina, Italy). Four spectroscopic techniques (X-ray Fluorescence, Raman, Attenuated Total Reflectance and Total Reflectance Infrared Spectroscopies) and six different spectrometers are tested to evaluate the impact of different setups. The novelty of the work is to use a systematic approach on this initial dataset using the entire spectroscopic energy range without any windows selection to solve problems linked with the manipulation of large analytes/materials to find an indistinct property of one or more spectral bands opening new frontiers in the dataset spectroscopic analyses.     

高功率半导体激光端面泵浦方形掺Nd3+离子激光晶体热形变研究

为了解决高功率半导体激光器端面泵浦激光晶体引起的热效应问题,激光晶体泵浦端面的热形变必须进行准确的计算.通过对于全固态激光器中激光晶体的工作特点分析,建立了矩形截面激光晶体热分析模型.基于热传导方程,提出了泊松方程的一种新解,并获得了矩形截面激光晶体端面热形变分布的一般解析表达式.同时讨论了半导体激光器偏心泵浦激光晶体给端面热形变带来的影响.与有限元分析方法以及其他数值分析方法相比,解析分析方法不会给计算引入任何的误差.热形变的解析分析为解决激光晶体的热效应问题以及提高激光器的性能提供了理论的依据.     

Chemometrics: An Excavator in Temperature-Dependent Near-Infrared Spectroscopy

Temperature-dependent near-infrared (NIR) spectroscopy has been developed and taken as a powerful technique for analyzing the structure of water and the interactions in aqueous systems. Due to the overlapping of the peaks in NIR spectra, it is difficult to obtain the spectral features showing the structures and interactions. Chemometrics, therefore, is adopted to improve the spectral resolution and extract spectral information from the temperature-dependent NIR spectra for structural and quantitative analysis. In this review, works on chemometric studies for analyzing temperature-dependent NIR spectra were summarized. The temperature-induced spectral features of water structures can be extracted from the spectra with the help of chemometrics. Using the spectral variation of water with the temperature, the structural changes of small molecules, proteins, thermo-responsive polymers, and their interactions with water in aqueous solutions can be demonstrated. Furthermore, quantitative models between the spectra and the temperature or concentration can be established using the spectral variations of water and applied to determine the compositions in aqueous mixtures.     

化学计量学在生命科学研究中的应用

对近十年来化学计量学在生命科学领域相关研究中的应用进行了综述,主要对其在DNA、蛋白质及氨基酸这三大生命物质有关研究中的使用展开了评述和讨论,参考文献59篇。