Practical liquid chromatography–tandem mass spectrometry method for the simultaneous quantification of amitriptyline,nortriptyline and their hydroxy metabolites in human serum

Amitriptyline (AMI) has been in use for decades in treating depression and more recently for the management of neuropathic pain. A highly sensitive and specific LC–tandem mass spectrometry method was developed for simultaneous determination of AMI, its active metabolite nortriptyline (NOR) and their hydroxy‐metabolites in human serum, using deuterated AMI and NOR as internal standards. The isobaric E‐10‐hydroxyamitriptyline (E‐OH AMI), Z‐10‐hydroxyamitriptyline (Z‐OH AMI), E‐10‐hydroxynortriptyline (E‐OH NOR) and Z‐10‐hydroxynortriptyline (Z‐OH NOR), together with their parent compounds, were separated on an ACE C₁₈ column using a simple protein precipitation method, followed by dilution and analysis using positive electrospray ionisation with multiple reaction monitoring. The total run time was 6 min with elution of E‐OH AMI, E‐OH NOR, Z‐OH AMI, Z‐OH NOR, AMI (+ deuterated AMI) and NOR (+ deuterated NOR) at 1.21, 1.28, 1.66, 1.71, 2.50 and 2.59 min, respectively. The method was validated in human serum with a lower limit of quantitation of 0.5 ng/mL for all analytes. A linear response function was established for the range of concentrations 0.5–400 ng/mL (r² > .999). The practical assay was applied on samples from patients on AMI, genotyped for CYP2C19 and CYP2D6, to understand the influence of metaboliser status and concomitant medication on therapeutic drug monitoring.     

Falcaria vulgaris leaf aqueous extract mediated synthesis of iron nanoparticles and their therapeutic potentials under in vitro and in vivo condition

In recent years, researchers have used bionanotechnology techniques as cost‐effective and eco‐friendly routes to fabricate nanoparticles. The present study confirms the ability of aqueous extract of Falcaria vulgaris for the biosynthesis of iron nanoparticles (FeNPs@F. vulgaris). Also, in this study, we showed the antioxidant, cytotoxicity, cutaneous wound healing, antibacterial, and antifungal activities of these nanoparticles. FeNPs@F. vulgaris were characterized by UV, FT‐IR, XRD, FE‐SEM, and TEM analysis. According to the XRD analysis, 25.3 nm was measured for the crystal size of nanoparticles. FE‐SEM and TEM images exhibited a uniform spherical morphology and average diameters of 25 nm for the biosynthesized nanoparticles. FTIR results offered protein and polysaccharides in F. vulgaris were the sources of reducing power, reducing iron ions to FeNPs@F. vulgaris. In vivo design, FeNPs@F. vulgaris ointment remarkably reduced (p ≤ 0.01) the wound area, total cells, neutrophil, and lymphocyte and substantially increased (p ≤ 0.01) the wound contracture, vessel, hydroxyl proline, hexosamine, hexuronic acid, fibrocyte, and fibrocytes/fibroblast rate compared to other groups in rats. Also, FeNPs@F. vulgaris indicated potential antioxidant activity against DPPH, antifungal potentials against Candida glabrata, Candida albicans, Candida krusei, and Candida guilliermondii, antibacterial properties against Gram‐positive bacteria (Streptococcus pneumonia, Staphylococcus aureus, and Bacillus subtilis) and Gram‐negative bacteria (Salmonella typhimurium, Pseudomonas aeruginosa, and Escherichia coli O157:H7) without any cytotoxicity effect against human umbilical vein endothelial cells. Finally, the results showed the useful antioxidant, non‐cytotoxic, cutaneous wound healing, antifungal, and antibacterial effects of FeNPs@F. vulgaris.     

Development and validation of an HPLC‐UV method for quantification of elvitegravir and two other new antiretrovirals,dolutegravir and rilpivirine,in the plasma of HIV‐positive patients

Therapeutic drug monitoring may be crucial in selected clinical conditions for the management of HIV infection. In recent years, new antiretrovirals have been introduced and in particular elvitegravir (EVG) is now recommended for first‐line and simplification treatment as well as dolutegravir (DTG) and rilpivirine (RPV). The aim of this study was to develop and validate a high‐performance liquid chromatography–ultraviolet (HPLC‐UV) method for determining EVG and new antiretrovirals DTG and RPV in human plasma. Solid‐phase extraction was applied to a 600 μL plasma sample. Chromatographic separation of the three drugs and internal standard was achieved with a gradient of acetonitrile and phosphate buffer on a C₁₈ reverse‐phase analytical column with a 20 min analytical run time. EVG and DTG were detected at 265 nm and RPV at 290 nm. Mean intra‐ and inter‐day precisions were < 10%; the mean accuracy was <15%. Extraction recovery ranged between 105 and 82% for the drugs analyzed. Calibration curves were optimized according to the expected ranges of drug concentrations in patients; the coefficient of determination was >0.997 for all drugs. This method allows for monitoring EVG, DTG and RPV in the plasma of HIV‐positive patients using HPLC‐UV.     

基于信任机制的战略联盟寿命周期研究

通过战略联盟的非合作博弈分析显示信任机制的重要性,并基于此在重复博弈过程中内生出战略联盟的寿命周期函数;研究结果表明在事后的道德风险问题情况下,战略联盟的寿命周期决定于一次性博弈中联盟成员战略选择及其交互影响下的效用水平;而在逆向选择问题情况下,战略联盟的预期寿命周期是社会平均信用水平、企业的耐性系数、不同策略组合下支付的函数。     

Pyridine Scaffolds,Phenols and Derivatives of Azo Moiety: Current Therapeutic Perspectives

Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure–activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.     

Comparison of LC-MS3 and LC-MRM Method for Quantifying Voriconazole and Its Application in Therapeutic Drug Monitoring of Human Plasma

The TDM of voriconazole which exhibits wide inter-individual variability is indispensable for treatment in clinic. In this study, a method that high-performance liquid chromatography tandem mass spectrometry cubed (HPLC-MS³) is first built and validated to quantify voriconazole in human plasma. The system is composed of Shimadzu Exion LC^TM UPLC coupled with a Qtrap 5500 mass spectrometer. The separation of voriconazole is performed on a Poroshell 120 SB-C18 column at a flow rate of 0.8 mL/min remaining 7 min for each sample. The calibration curves are linear in the concentration range of 0.25–20 μg/mL. Intra-day and inter-day accuracies and precisions are within 8.0% at three concentrations, and the recoveries and matrix effect are all within accepted limits. In terms of stability, there is no significant degradation of voriconazole under various conditions. The HPLC-MS³ and HPLC-MRM (multiple reaction monitoring) methods are compared in 42 patients with Passing–Bablok regression and Bland–Altman plots, and the results show no significant difference between the two methods. However, HPLC-MS³ has a higher S/N (signal-to-noise ratio) and response than the MRM. Finally, the HPLC-MS³ assay is successfully applied to monitor the TDM (therapeutic drug monitoring) of voriconazole in human plasma, and this verifies that the dosing guidelines for voriconazole have been well implemented in the clinic and patients have received excellent treatment.     

Development and Validation of a Highly Sensitive and Rapid LC-MS3 Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring

A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS³) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in combination with protein precipitation extraction for sample pretreatment has been developed and validated for the simultaneous determination of the antiepileptic drug oxcarbazepine (OXC) and its main active metabolite (MHD) in human serum. The separation was performed on a Waters XBridge BEH C18 column (2.5 µm, 2.1 × 50 mm) in isocratic elution with 0.1% formic acid in water and methanol (50:50, v:v) as the mobile phase. The run time for each sample was 2.0 min. The calibration curves ranging from 25 to 1600 ng/mL for OXC and from 0.5 to 32 μg/mL for MHD showed correlation coefficients (r) better than 0.99. All of the validation data, such as precision, accuracy and other parameters, fit the requirements of the current bioanalytical method validation guidelines. The LC-MS³ method for quantitation of OXC and MHD was compared with the LC-MRM based method. Passing–Bablok regression coefficients and Bland–Altman plots showed that the developed LC–MS³ method is a reliable method for quantitative analysis of OXC and MHD. The proposed LC-MS³ method was successfully applied to determine the serum concentrations of OXC and MHD to support a clinical study.     

Potential Therapeutic Approach of Melatonin against Omicron and Some Other Variants of SARS-CoV-2

The Omicron variant (B.529) of COVID-19 caused disease outbreaks worldwide because of its contagious and diverse mutations. To reduce these outbreaks, therapeutic drugs and adjuvant vaccines have been applied for the treatment of the disease. However, these drugs have not shown high efficacy in reducing COVID-19 severity, and even antiviral drugs have not shown to be effective. Researchers thus continue to search for an effective adjuvant therapy with a combination of drugs or vaccines to treat COVID-19 disease. We were motivated to consider melatonin as a defensive agent against SARS-CoV-2 because of its various unique properties. Over 200 scientific publications have shown the significant effects of melatonin in treating diseases, with strong antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has a high safety profile, but it needs further clinical trials and experiments for use as a therapeutic agent against the Omicron variant of COVID-19. It might immediately be able to prevent the development of severe symptoms caused by the coronavirus and can reduce the severity of the infection by improving immunity.     

网络环境下图书馆联盟与资源共享探析

阐述了网络环境下建设图书馆联盟的重要意义,对图书馆联盟的概念、形式、类型、意义和茇展趋势进行分析,并提出了我国图书馆联盟建设的策略。     

知识共享对战略联盟绩效影响的研究

研究采用文献分析法和问卷调查法,分析知识共享对战略联盟绩效的影响。通过归纳总结大量国内外文献,建立知识共享对战略联盟绩效影响模型,并在欧盟50家制造企业中进行了问卷调查。应用SPSS软件对数据进行了信度效度分析,并通过相关分析和回归分析对假设进行检验。回归分析的结果表明:自变量联盟之间的信任、知识共享隐含性和知识相关性对联盟绩效有重大影响;控制变量中学习和联盟经验对联盟绩效有影响。