A gadolinium-based magnetic ionic liquid for supramolecular dispersive liquid–liquid microextraction followed by HPLC/UV for the determination of favipiravir in human plasma

Favipiravir is a potential antiviral medication that has been recently licensed for Covid-19 treatment. In this work, a gadolinium-based magnetic ionic liquid was prepared and used as an extractant in dispersive liquid–liquid microextraction (DLLME) of favipiravir in human plasma. The high enriching ability of DLLME allowed the determination of favipiravir in real samples using HPLC/UV with sufficient sensitivity. The effects of several variables on extraction efficiency were investigated, including type of extractant, amount of extractant, type of disperser and disperser volume. The maximum enrichment was attained using 50 mg of the Gd-magnetic ionic liquid (MIL) and 150 μl of tetrahydrofuran. The Gd-based MIL could form a supramolecular assembly in the presence of tetrahydrofuran, which enhanced the extraction efficiency of favipiravir. The developed method was validated according to US Food and Drug Administration bioanalytical method validation guidelines. The coefficient of determination was 0.9999, for a linear concentration range of 25 to 1.0 × 10⁵ ng/ml. The percentage recovery (accuracy) varied from 99.83 to 104.2%, with RSD values (precision) ranging from 4.07 to 11.84%. The total extraction time was about 12 min and the HPLC analysis time was 5 min. The method was simple, selective and sensitive for the determination of favipiravir in real human plasma.     

Biodistribution study of free and microencapsulated 6‐methylcoumarin in Wistar rats by HPLC

A sensitive, specific and reproducible HPLC method has been developed and validated for the quantitative determination of 6‐methylcoumarin (6MC) in plasma and other tissues in Wistar rats. A C₁₈ column was used with UV detection at 321 nm and a gradient system consisting of methanol‐deionized water was used as mobile phase. The retention time for 6MC was 14.921 min and no interfering peaks were observed for any of the matrices. Linear relationships (r² > 0.997) were obtained between the peak height ratios and the corresponding biological sample concentrations over the range 0.4–12.8 µg/mL. Precision and accuracy were evaluated; the coefficient of variation and the relative error for all of the organs were <2 and 7%, respectively. The limit of quantitation was 0.20 µg/mL for the heart and 0.30 µg/mL for the other tissues evaluated. This HPLC method was successfully used in the determination of 6MC in the biodistribution study after administration of 200 mg/kg of both 6MC‐free and 6MC‐loaded polymeric microparticles. In this study, extensive 6MC was found, in both free and microencapsulated forms, in all the organs tested. The 6MC‐free showed a range of between 1.7 and 11.5 µg/g, while the microencapsulated 6MC showed concentrations of between 6.35 and 17.7 µg/g, suggesting that 6MC improved absorption rate. Copyright © 2014 John Wiley & Sons, Ltd.     

A dried blood spot assay with HPLC–MS/MS for the determination of larotrectinib in mouse blood and its application to a pharmacokinetic study

Larotrectinib is a first-generation tropomyosin kinase inhibitor, approved for the treatment of solid tumors. In this paper, we present a validated dried blood spot (DBS) method for the quantitation of larotrectinib from mouse blood using HPLC–MS/MS, which was operated under multiple reaction monitoring mode. To the DBS disc cards, acidified methanol enriched with internal standard (IS; enasidenib) was added and extracted using tert-butyl methyl ether as an extraction solvent with sonication. Chromatographic separation of larotrectinib and the IS was achieved on an Atlantis dC₁₈ column using 10 mm ammonium formate–acetonitrile (30:70, v/v) delivered at a flow-rate of 0.80 ml/min. Under these optimized conditions, the retention times of larotrectinib and the IS were ~0.93 and 1.37 min, respectively. The total run time was 2.50 min. Larotrectinib and the IS were analyzed using positive ion scan mode and parent–daughter mass to charge ion (m/z) transitions of 429.1 → 342.1 and 474.1 → 267.1, respectively, were used for the quantitation. The calibration range was 1.06–5,080 ng/ml. No matrix effect or carryover was observed. Hematocrit did not influence DBS larotrectinib concentrations. All of the validation parameters met the acceptance criteria. The applicability of the validated method was shown in a mouse pharmacokinetic study.     

2008—2012年《中华实用儿科临床杂志》载文文献计量分析

目的:分析《中华实用儿科临床杂志》近5年发展情况,为提高该刊质量提供参考依据. 方法:通过"中国生物医学文献数据库"收集该刊2008—2012年的文献题录,采用文献计量学方法,对文献的时间分布、单位分布、作者分布、作者合作情况、单位合作情况、高频关键词、高频主题词等指标进行统计分析. 结果:2008—2012年《中华实用儿科临床杂志》共载文3 459篇,单篇论文的长度在逐年增长;涉及作者13 870位,每篇论文作者平均数量大于4,每篇论文的平均合作单位数量多于1.45,关键词和主题词符合本刊的主题.2008—2010年被引的文献为1 131条,占期间总文献量的62%.结论:2008—2012年发表的论文选择更具有针对性,向着更为合理性的方向发展,研究方法也多采用定量分析方法,并且论文形式多样,文献被引次数越来越多.     

HPLC with fluorescence detection assay of perampanel,a novel AMPA receptor antagonist,in human plasma for clinical pharmacokinetic studies

Perampanel (Fycompa®), a novel α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonist, is registered for the adjunctive treatment of patients (aged ≥12 years) with refractory partial‐onset seizures. To support therapeutic drug monitoring, a simple high‐performance liquid chromatography (HPLC) assay with fluorescence detection was developed to determine perampanel concentrations in human plasma and validated to support clinical trials. Human plasma samples (1.0 mL) were processed by liquid extraction using diethyl ether, followed by chromatographic separation on a YMC Pack Pro C₁₈ column (150 × 4.6 mm i.d., 5 µm) with isocratic elution of acetonitrile–water–acetic acid–sodium acetate (840:560:3:1.8, v/v/v/w) at a flow rate of 1.0 mL/min. Column eluent was monitored at excitation and emission wavelengths of 290 and 430 nm, respectively. The assay was linear (range 1.0–500 ng/mL) and this could be extended to 25 µg/mL by 50‐fold dilution integrity. No endogenous peaks were detected in the elution of analytes in drug‐free blank human plasma from six individuals and no interference was observed with co‐medications tested. Intra‐ and inter‐batch reproducibility studies demonstrated accuracy and precision within the acceptance criteria of bioanalytical guidelines. Validation data demonstrated that our assay is simple, selective, reproducible and suitable for therapeutic drug monitoring of perampanel. Copyright © 2015 John Wiley & Sons, Ltd.     

科技论文中“关键词”的标引方法

从关键词在文献检索中的重要作用论述了科技论文的发表，必须重视关键词的标引．明确指出出版专业中关键词的概念，探讨了不同标引方法的利弊，介绍了关键词的标引方法．     

用正交试验法确定最佳调剖施工参数

针对文明寨油田地质特征和开采现状，按照油藏数值模拟原理，以调剖井对应油井的增油降水创经济效益大小为考核指标，运用正交试验的均衡分散性和整齐可比性及Ｌ９（３４），正交表进行调剖最佳施工参数试验．经现场试验、分析、讨论发现：影响调剖效果的主要因素是措施半径，其次为施工排量和注入方式，且最佳施工参数是措施半径在３．５ｍ左右，施工排量在１９ｍ３／ｈ左右，按连续注入方式调剖。经文明察油田、卫城油田、马寨油田５０井次现场试验证明，较好地改善了注水井吸水剖面，对应油井取得了明显的增油降水效果，收到了较好的经济和社会效益．     

Locally Periodic Versus Globally Periodic Infinite Words

We call a one-way infinite word w over a finite alphabet (ρ,l)-repetitive if all long enough prefixes of w contain as a suffix a ρth power (or more generally a repetition of order ρ) of a word of length at most l. We show that each (2,4)-repetitive word is ultimately periodic, as well as that there exist continuum many, and hence also nonultimately periodic, (2,5)-repetitive words. Further, we characterize nonultimately periodic (2,5)-repetitive words both structurally and algebraically.     

高效液相色谱法测定复方盐酸普莫卡因乳膏含量

目的建立高效液相色谱法(HPLC)测定复方盐酸普莫卡因乳膏含量的方法。方法选用CLC-ODS C18色谱柱(150 mm×4.6 mm,5μm),流动相为乙腈-磷酸盐缓冲液(55∶45,体积比)调节pH值为7.5,流速为1.0 mL/min,柱温为40℃,检测波长为224 nm。结果盐酸普莫卡因在0.212 0~0.903 5 mg/mL范围内浓度与峰面积呈良好线性关系(r=0.999 9),平均回收率为99.63%,RSD为0.53%。结论该法简便、快速、可靠,可用于复方盐酸普莫卡因乳膏的质量控制。     

The structure of invertible substitutions on a three-letter alphabet

We study the structure of invertible substitutions on three-letter alphabet. We show that there exists a finite set of invertible substitutions such that any invertible substitution can be written as I_wσ₁σ₂σ_k, where I_w is the inner automorphism associated with w, and for 1jk. As a consequence, M is the matrix of an invertible substitution if and only if it is a finite product of non-negative elementary matrices.