HPLC Assay for S-2-(3-Aminopropylamino)ethyl Phosphorothioate (WR 2721) in Plasma

Abstract

A specific HPLC assay has been developed for determination of the radioprotective drug WR 2721. The method is based on precolumn derivatization of plasma with fluorescamine, separation with a C-18 cartridge and detection by fluorescence. An external standard was used for calibration, and values were adjusted based upon recovery of added ¹⁴C-labeled WR 2721. WR 2721 had a retention time of about 13 minutes using a mobile phase of acetonitrile/water (22:78), 0.01 M in dibutylammonium phosphate, at a flow rate of 2 mL/min. Sensitivity of the assay was characterized to 2 μg/mL, and detector response was linear over the range of 2 to 1100 μg/mL. The assay requires 90 μL of plasma and has a total chromatography time of about 45 minutes. 2-(3-Aminopropylamino)ethanethiol (WR 1065) and bis- [2- (3-aminopropylamino)ethyl]disulfide (WR 33278), metabolites of the drug, and a variety of primary amines were shown not to interfere with the assay. Suitability of this assay for pharmacokinetic studies was demonstrated in preliminary experiments with a beagle dog.     

A Liquid Chromatographic Electrochemical Assay for S-2-(3-Aminopropylamino) Ethylphosphorothioate (WR2721) in Human Plasma

Abstract

A liquid chromatographic electrochemical method for the determination of the radioprotective drug WR2721 in human plasma has been developed. This method includes the use of a Hg/Au electrochemical detector for the direct measurement of WR2721 concentration. An analog of WR2721, S-3-{4-aminobutylamino} propylphosphorothioate (WR80855) is the internal standard. The retention times for WR2721 and WR80855 are approximately 4.5 and 9 minutes, respectively. WR1065, the free sulfhydryl metabolite of WR2721, is retained on the column under the described chromatographic conditions and therefore does not interefere with the determination of the parent drug. With modification of the mobile phase WR1065 is eluted from the column at a retention time of approximately 20 minutes. This method has good linearity, precision and accuracy, and is free from interference from endogenous plasma substances. Preliminary results showing the applicability of this method to human pharmacokinetic studies and to investigating the enzymatic hydrolysis of WR2721 are presented.     

A Method for the Measurement of total Drug Convertible to Cysteamine: Application to Pharmacokinetic Experiments with Ethiofos

Abstract

An analytical method has been developed for the quantification of cysteamine (2-aminoethanethiol) in plasma. A reductive sample pretreatment is used to convert disulfide-bound cysteamine to the free thiol which is subsequently separated by HPLC and detected by electrochemical detection (LCEC). The method was developed to follow drug disposition after administration of ethiofos (WR-2721, S-2-(3-aminopropylamino) ethyl phosphorothioic acid) and WR-1065 (2-(3-aminopropylamino)ethanethiol). Standard calibration curves were linear over the range 0.01- to 25.0 /μg/mL (0.130-324 μM) and a minimum detectable quantity of 0.01 μg/mL was calculated at a signal-to-noise ratio of 3. Assay precision over the same range averaged 2% (coefficient of variation) and relative recovery, used as a measure of accuracy, was 100Z. Stability of cysteamine in plasma, relative to an internal standard (2-aminopropanethiol, WR-186) was good; stored samples were found to contain an average of 94.6 ± 10.4z of the original cysteamine concentration following 28 days at -75 °C.

This method was successfully applied in dosing experiments with rhesus monkeys in which ethiofos was administered into the cephalic vein (IV), portal vein (P) and duodenum. In IV experiments total VR-1065 plasma concentrations greatly exceeded total cysteamine concentrations. While results indicate formation of free and bound cysteamine is not a major metabolic pathway of ments total VR-1065 plasma concentrations greatly exceeded total cysteamine concentrations. While results indicate formation of free and bound cysteamine is not a major metabolic pathway of ethiofos, increased levels of bound cysteamine were observed.     

Identification Of Oxygen Derivatives Of Polycyclic Aromatic Hydrocarbons In Airborne Participate Matter Of Upper Silesia (Poland)

Abstract

Organic material extracted from airborne participate matter collected in various places of Upper Silesia has been separated by column liquid adsorption chromatography. Six fractions of different polarity have been eluted. These fractions have undergone careful spectral analysis, thin layer chromatography and gas chromatography-mass spectrometry. Several PAH oxygen derivatives which have not been found in air from our Region so far were identified. Their biological activity is higher than activity of basic PAH structures. These compounds can be responsible to a high degree for interference in living organism functions in this highly polluted region.     

Measurement of the amount of information contained in a chemical equation (Preliminary estimation)

The entropy of chemical language was estimated basing on Shannon’s theory of information. The alphabet of the language was defined. It contains 110 symbols of chemical elements, indices, coefficients, brackets, condition signs, and some other (a total of 166 symbols). The probabilities of the symbols were calculated using a higher school chemistry textbook. The upper bound of entropy of chemical language was estimated at 4.55 bits per symbol. The table of frequencies and self-information for the language was given, and the way to calculate the amount of information was shown.     

A Simple Microdetermination Of Polymer Flocculants (Polyacrylamides And Guar) In Mine Water

Abstract

An extremely simple, sensitive and selective microdetermination of polymer flocculants in mine water is feasible by measuring the laminar flow rate through membrane filter under vacuum.     

尺寸排阻色谱-电感耦合等离子体质谱联用研究比格犬血浆中米铂及铂代谢物形态

建立了基于尺寸排阻色谱-电感耦合等离子体质谱联用( SEC-ICP-MS)分析比格犬血浆中米铂及其铂代谢物形态的方法。半定量测得的血浆中总铂的含量与传统ICP-MS直接测定方法基本相同。采用Bio-Sep-s2000型色谱柱在25 mmol/L磷酸盐缓冲液(pH 7.2)的色谱条件下与ICP-MS联用检测同位素Pt-195发现,血浆中有米铂原型和4种铂代谢物;将不同时间点采集的血浆进行铂形态分析发现,与蛋白结合的铂代谢物m2含量最高;米铂不与血浆蛋白结合。对比米铂与m2的相对含量发现,米铂原型与m2的比例在给药初期迅速下降,后缓慢上升,再随血药浓度的下降而缓慢下降。     

CZE Determination of Mismatched Double-Stranded Oligonucleotides (poly I:poly C12U) in Beagle Serum

A capillary zone electrophoretic (CZE) method with diode-array detection has been established for analysis of mismatched double-stranded oligonucleotides, poly I:poly C₁₂U, in beagle serum. The effects of sample pretreatment, buffer pH, buffer concentration, and applied voltage on the separation of inosine were optimized. Baseline separation was obtained for inosine within 11 min by use of 0.05 mol L^?1 borate running buffer, pH 9.60, and an applied voltage of 25 kV at 25 °C; the detection wavelength was 254 nm. To evaluate the performance of the method and demonstrate the utility of the approach, an experiment was designed in which poly I:poly C₁₂U were added to serum at different concentrations, artificially creating groups of samples. The proposed CZE method seemed a powerful technique for kinetic study of poly I:poly C₁₂U in serum.     

CZE Determination of Mismatched Double-Stranded Oligonucleotides (poly I:poly C12U) in Beagle Serum

A capillary zone electrophoretic (CZE) method with diode-array detection has been established for analysis of mismatched double-stranded oligonucleotides, poly I:poly C₁₂U, in beagle serum. The effects of sample pretreatment, buffer pH, buffer concentration, and applied voltage on the separation of inosine were optimized. Baseline separation was obtained for inosine within 11 min by use of 0.05 mol L⁻¹ borate running buffer, pH 9.60, and an applied voltage of 25 kV at 25 °C; the detection wavelength was 254 nm. To evaluate the performance of the method and demonstrate the utility of the approach, an experiment was designed in which poly I:poly C₁₂U were added to serum at different concentrations, artificially creating groups of samples. The proposed CZE method seemed a powerful technique for kinetic study of poly I:poly C₁₂U in serum.

     

The Potential Response Of Copper(Ii) Sulfide Ion Selective Electrode To Hg(Ii) Ions In Aqueous Solution

Abstract

The application of a cupric ion-selective electrode with a membrane of mixed Ag₂S-CuS to measure the activity of Hg(II) is presented. The linear electrode response curve which covers near three decades, from 10^?5 to 10^?2 mol dm^?3, of mercuric concentration range was obtained, under background of acetate buffer.     

A Rapid Qualitative Method For The Detection Of Monofluoroacetic Acid (1080) In Liquid Baits

Abstract

A rapid, simple, and sensitive method for detecting the rodenticide monofluoroacetic acid (1080) in liquid baits is described. Sensitivity is in the ppm region and the method can be completed in about 15 minutes.     

LC Determination of Helicidum in Beagle Dog Plasma: Study on the Pharmacokinetics of Helicidum Orally Disintegrating Tablets Compared to Conventional Tablets

A sensitive and reproducible liquid chromatographic method with UV detection was described for the determination of helicidum in beagle dog plasma. Sample preparation was accomplished through protein precipitation with 15% perchloric acid and chromatographic separation was performed on a reversed phase C₁₈ column at 30 °C. Mobile phase consisted of a mixture of acetonitrile–water at a flow rate of 1.0 mL min^?1. Wavelength was set at 270 nm. The method was applied to a pharmacokinetic study of two formulations of helicidum. No statistical difference in the t _1/2 (AUC_0–5, AUC_0–∞) between the two formulations were observed. The t _max of helicidum ODTs is significantly shorter than that of conventional tablets (0.84 h vs. 1.33 h, P< 0.05).     

LC Determination of Helicidum in Beagle Dog Plasma: Study on the Pharmacokinetics of Helicidum Orally Disintegrating Tablets Compared to Conventional Tablets

A sensitive and reproducible liquid chromatographic method with UV detection was described for the determination of helicidum in beagle dog plasma. Sample preparation was accomplished through protein precipitation with 15% perchloric acid and chromatographic separation was performed on a reversed phase C₁₈ column at 30 °C. Mobile phase consisted of a mixture of acetonitrile–water at a flow rate of 1.0 mL min⁻¹. Wavelength was set at 270 nm. The method was applied to a pharmacokinetic study of two formulations of helicidum. No statistical difference in the t _1/2 (AUC_0–5, AUC_0–∞) between the two formulations were observed. The t _max of helicidum ODTs is significantly shorter than that of conventional tablets (0.84 h vs. 1.33 h, P< 0.05).

     

离子色谱法（安培检测器）测定血清、尿及头发中微量碘

This paper intreduces a reasonable pretreatment method for IC-amperometric method employed to measuretrace amount of iodine in serum, urine and hair. The resultant graph is simple and clear,and withoutinterference in a general way. The limits of detection for iodine in serum,urine and hair are 0.007,0.003μg/mL and 0. 046μg/g, respectively.The recovery of iodine added into the sample is 82～93%. The coefficient ofvariation is less than 9%. Trace amount of bromine in the sample can also be measured simultan     

Cu(In,Ga)Se_2薄膜组成表面分析准确测量国际关键比对

中国计量科学研究院参加了国际关键比对K129,采用X射线光电子能谱仪(XPS)建立了测量薄膜太阳能电池材料铜铟镓硒(CIGS)薄膜组成和深度成分分布的有效方法。采用合适的条件,对CIGS薄膜进行深度剖析,提出并完善了一套XPS深度剖析数据处理方法(全计数法和相对灵敏度因子法),对薄膜组成进行了准确测量。结果表明,该方法的测量重复性良好,5次测量的相对标准偏差(RSD)均小于2%,测量扩展不确定度优于4%,与其他国家计量院的结果取得等效一致。对比研究了不同灵敏度因子来源(由参考样品获得、仪器数据库的3种来源)对CIGS薄膜组成测量结果的影响,结果表明,仪器厂商数据库自修正的灵敏度因子最接近于参考样品,可较好地对CIGS薄膜进行原子含量测量。该方法可推广用于表面分析设备深度剖析薄膜样品时定量计算薄膜成分,提高测量薄膜成分的准确度,为薄膜太阳能电池材料研发和产业化提供参考依据。     

Electronic properties of Si and Ge atoms doped in clusters: In(n)Si(m) and In(n)Ge(m)

Electronic properties of silicon and germanium atom doped indium clusters, In(n)Si(m) and In(n)Ge(m), were investigated by photoionization spectroscopy of the neutrals and photoelectron spectroscopy of the anions. Size dependence of ionization energy and electron affinity for In(n)Si(1) and In(n)Ge(1) exhibit pronounced even-odd alternation at cluster sizes of n = 10-16, as compared to those for pure In(n) clusters. This result shows that symmetry lowering with the doped atom of Si or Ge results in undegeneration of electronic states in the 1d shell formed by monovalent In atoms.     

超高效液相色谱-串联质谱法测定犬血浆中利培酮和帕潘立酮及药代动力学研究

建立了超高效液相色谱-串联质谱法(UPLC-MS/MS)测定犬血浆中利培酮和帕潘立酮的浓度.血浆样品用乙腈沉淀蛋白后,用Zorbax SB-C18柱分离,以乙腈-10 mmol/L乙酸铵溶液(65∶35,V/V)为流动相,在电喷雾离子源正离子模式下以多反应监测(MRM)方式进行检测.利培酮、帕潘立酮分别在0.05～30.0 ng/mL和0.10～30.0 ng/mL范围内线性关系良好(r2＞0.99),定量限分别为0.05 ng/mL和0.10 ng/mL,回收率分别为91.2％～95.1％和93.1％～97.5％.该方法精密、准确、快速,适用于临床血药浓度的监测及利培酮缓释微球药动学的研究.     

Simultaneous Estimation of Vinpocetine and Its Metabolite, Apovincaminic Acid, in Beagle Plasma by LC-MS-MS

A method was developed to determine vinpocetine and its metabolite, apovincaminic acid, in beagle plasma by LC-MS-MS. After protein precipitation with methanol, the supernatant of the sample was concentrated and injected into an Agilent Zorbax XDB-C₁₈ column. The sample was separated by a mobile phase consisting of acetonitrile and 0.2% formic acid solution, and the reading was determined on an Agilent 6410 Triple Quad Tandem mass spectrometer in multiple reaction monitoring mode with the following transitions: m/z 351.5 ?? 280.2/266.3 for vinpocetine, 323.2 ?? 236.1/280.2 for apovincaminic acid, and 411.2 ?? 191.1 for the internal standard. The intra- and inter-day variances were less than 15% (RSD%), and average recoveries were higher than 80%. The linearity ranges (LR) between 0.1 and 20.0 ng mL^?1 for vinpocetine (r ² = 0.9980) and between 1.0 and 200.0 ng mL^?1 for apovincaminic acid (r ² = 0.9995) were established. In summary, this method is sensitive, specific, and appropriate for in vivo study of various dosage forms of vinpocetine.     

Macromolecular Crowding Agents‐Assisted Imprinted Polymers For Analysis Of Glycocholic Acid In Human Plasma And Urine

Glycocholic acid (GCA) is a newly identified biomarker for hepatocellular carcinoma (HCC) patients. In this study, a method based on macromolecular crowding strategy has been applied for preparation of a molecularly imprinted polymer (MIP), which possesses high adsorption capacity for GCA. Polymethyl methacrylate was used as a macromolecular crowding agent, N‐(3‐aminopropyl)‐methacrylamide hydrochloride as a functional monomer and ethylene dimethacrylate as a cross‐linker. The morphology and binding characteristics of MIP were assessed by scanning electron microscopy and absorption experiments. The MIP was used as an adsorbent material to separate GCA, and the molecularly imprinted solid‐phase extraction (MISPE) was carefully optimized. The MISPE combined with high‐performance liquid chromatographic analysis was successfully used to determine the GCA in plasma and urine samples. When spiked levels ranged from 0.2 to 20 μmol L^?1, the recoveries were between 94.3 and 100.5%. As a proof of principle, this proposed method has been validated on a small subset of HCC patients (n = 10) and healthy volunteers (n = 10). The average GCA concentrations of HCC patients in plasma and urine were about 25 and 2.8 times than that of healthy volunteers. Copyright © 2016 John Wiley & Sons, Ltd.