Rapid, simultaneous determination of lopinavir and ritonavir in human plasma by stacking protein precipitations and salting-out assisted liquid/liquid extraction, and ultrafast LC-MS/MS

Lopinavir and ritonavir are co-formulated in Kaletra^® approved for the treatment of human immunodeficiency virus infection. A validated analytical method is mandatory for clinical development and therapeutic drug monitoring. Here we are reporting a method for rapid, simultaneous determination of lopinavir and ritonavir in human plasma with stacked protein precipitations and salting-out assisted extraction (SALLE), and ultrafast LC-MS/MS detection. With stacked protein precipitations and SALLE, the sample preparation for a 96-well plate can be completed within 20 min by an automated pipette. Due to the unique cleanliness of SALLE extracts post double protein precipitations, the extracts were injected into an ultrafast liquid chromatography and tandem mass spectrometry system (LC-MS/MS) after simple dilution. An Agilent Zobax Extend-C18 Rapid resolution HT column (1.8 μm, 2.1 mm × 30 mm) was used for the separation. A mixture of acetonitrile:water (55:45, v/v) with 0.1% formic acid was used as the mobile phase. LC ran for approximately 48 s at a flow rate of 0.5 mL min⁻¹, tandem mass spectrometric data collection started at 15 s and lasts for 30 s. The method was validated with reference to Industry Guidance for Bioanalytical Method Validation and then used for clinical samples. The method is ultrafast, and robust. Results of incurred samples demonstrated excellent method of reproducibility. This ultrafast analysis speed did not compromise with the data quality. To our knowledge, this is the fastest analytical method for simultaneous determination of lopinavir and ritonavir.     

Determination of trace impurities in high-purity iron using salting-out of polyoxyethylene-type surfactants

To an iron sample solution was added polyoxyethylene-4-isononylphenoxy ether (PONPE, nonionic surfactant, average number of ethylene oxides 7.5) and the surfactant was aggregated by the addition of lithium chloride. The iron(III) matrix was collected into the condensed surfactant phase in >99.9% yields, leaving trace metals [e.g., Ti(IV), Cr(III), Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Pb(II), and Bi(III)] in the aqueous phase. After removing the surfactant phase by centrifugation, the remaining trace metals were concentrated onto an iminodiacetic acid-type chelating resin. The trace metals were desorbed with dilute nitric acid for the determination by inductively coupled plasma-mass spectrometry or graphite-furnace atomic absorption spectrometry. The proposed separation method allowed the analysis of high-purity iron metals for trace impurities at low μg g⁻¹ to ng g⁻¹ levels.     

光度法及离子色谱法测定驱油剂中硫酸根含量——联合运用盐析法及活性炭吸附法除去其复杂有机物基体干扰

提出了一种简单、快速的盐析与活性炭吸附混合法,用于去除铬酸钡光度法及离子色谱法测定驱油剂中硫酸根时复杂的有机物基体干扰。考察了样品处理方法、盐种类、盐用量、活性炭用量对基体去除效果的影响。发现使用盐析与活性炭吸附混合法且盐、活性炭质量浓度分别为60,40g·L~(-1)时具有最佳的去除基体干扰效果。方法用于5种驱油剂样品的预处理,并与铬酸钡间接光度法及离子色谱结合用于硫酸根的测定,两种方法测定结果吻合良好。     

氯盐溶液中甲烷水合物高压分解条件及影响因素

向水合物储层注入盐类溶液是水合物常规开采技术之一,所以必须掌握储层压力条件下盐类溶液中水合物分解条件及其影响因素.本文研究了NaCl、MgCl2、CaCl2氯盐溶液中甲烷水合物分解条件,结果表明NaCl(2.0、1.0、0.5 mol·L-1)、MgCl2 (1.0、0.5 mol·L-1)和CaCl2 (1.0、0.5 mol·L-1)溶液中甲烷水合物的分解温度比纯水中分别降低了(4.8、2.4、1.0 K (NaCl))、(5.3、1.5 K (MgCl2))和(4.3、1.8 K (CaCl2)).以van der Waals 和Platteeuw 热力学模型为基础,结合电解质溶液中水的活度方程(Pitzer-Mayorga 方程),给出了氯盐溶液中水合物分解条件热力学模型,进而比较了模型计算值与实验值,结果显示两者非常吻合.分析表明,氯盐溶液中离子静电作用产生的水分子溶剂化效应和盐析效应降低了水的活度而导致水合物分解温度降低.