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Clinical Detection of Exposure to Chemical Warfare Agents *
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
Benedict R. Capacio, J. Richard Smith, Robert C. diTargiani, M. Ross Pennington, Richard K. Gordon, Julian R. Haigh, John R. Barr, Brian J. Lukey, Daniel Noort
A number of additional methods have been developed for the trace-level analysis of TDG and/or TDGO in urine (Black and Read, 1988, 1995a; Boyer et al., 2004; Jakubowski et al., 1990; Riches et al., 2007). There are a number of characteristics that are common to all of the methods. They all use GC in association with some form of MS for the analysis, use a derivatizing agent to make the analyte more amenable to GC analysis and to increase sensitivity, and incorporate an isotopically labeled form of TDG as an internal standard. Most of the methods use a solid phase extraction cartridge for sample preparation. Some of the methods incubate the urine samples with glucuronidase with sulfatase activity to release any glucuronide-bound conjugates. Some of the methods use titanium trichloride (TiCl3) in hydrochloric acid to reduce TDGO to TDG. The strong acid also appears to hydrolyze acid-labile esters of TDG and TDGO. Ultimately, each of the methods will convert all target analytes into the single analyte TDG for analysis. All of the methods have similar limits of detection, approximately 0.5–1 ng/mL. While an assay has been developed for the analysis of TDGO separately without a conversion to TDG, the method is complicated by the high polarity of the analyte (Black and Read, 1991a). Consequently, the use of the reducing agent TiCl3 has been the more common approach.
Pitfalls and Practical Solutions
Published in Joseph Chamberlain, The Analysis of Drugs in Biological Fluids, 2018
Because of the greater variety of phases that can be used for solid phase extraction, and the variety of solvents, buffers and other solutions that can be used in the elution sequences, the technique of solid-phase extraction is considerably more versatile than traditional methods, but the corollary of this is that the analyst must be well informed on the mechanism of all the interactions and secondary interactions if he is to maintain proper control of the separations. However, because of the ready analysis of drugs by HPLC, it is possible to use HPLC retention data to predict the behavior of drugs on extraction cartridges which use the same stationary phase, as described by Casas el al.1431,1432 for benzodiazepines. Those authors suggested that in general, C2 phases are best for benzodiazepines in extracting fewer extraneous peaks from urine and plasma than C8 or C18.1431
Using Appropriate Methodology and Technology for Research and Development of African Traditional Medicines
Published in Charles Wambebe, African Indigenous Medical Knowledge and Human Health, 2018
Rasoanaivo Philippe, Merlin Wilcox, Bertrand Graz
The first three factors refer to bioassay-guided fractionation, which requires a strong collaboration between a biologist and a chemist, such that the desired active compounds are obtained efficiently. Extraction is the first step in the study of medicinal plants, because it is necessary to extract the desired chemical components from the plant materials for further investigation. The selection of a solvent system largely depends on the specific nature of the bioactive compound being targeted. If the plant is selected on the basis of traditional uses, then it is necessary to prepare the extract according to the traditional recipe. Different solvent systems are also available to extract the bioactive compound from natural sources. Other modern extraction techniques are also available, namely, solid-phase micro-extraction, supercritical-fluid extraction, pressurized-liquid extraction, microwave-assisted extraction, solid-phase extraction, and surfactant-mediated techniques, which possess certain advantages over traditional methods (Sticher, 2008). In bioassays, models have moved from a holistic approach using humans and later on animal models (also called multitarget functional bioassays) toward a reductionist approach (also called single-target specific bioassays) with enzymatic or receptor binding techniques that can be done at a nanoscale level (Figure 4.1).
Liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for determination of free and total dabigatran in human plasma and its application to a pharmacokinetic study
Published in Drug Development and Industrial Pharmacy, 2021
Khurshid Shaikh, Ashish Mungantiwar, Supriya Halde, Nancy Pandita
The method established with solid-phase extraction was found to be the optimum approach to achieve consistent recovery of the analyte and IS. The expected recovery may not be 100%, however, the degree to recover the analyte and IS should be consistent and expected results should be precise. Recovery was accepted when the precision (% CV) of the analyte and IS (at each QC level) was ≤15.0%. Results indicated the combined matrix effect and recovery competence. The mean recovery was obtained above 83.3%, 89.1%, and 91.6% for DAB (free), DAB (total) and DAB-D4 respectively supporting the precision between 0.81 and 3.07%. The % difference recovery of hemolysed and lipemic plasma with respect to plain plasma was less than 4.85% and 1.08% for the analyte and IS respectively. The recoveries of DAB (free), DAB (total) and DAB-D4 from human plasma following solid-phase extraction are summarized in (Table 1a–1c) respectively. These results indicated were consistent and adequate throughout the studied concentration range and the fitness of the selected compound as IS to correct for possible inconsistency in dilutions, recovery, adsorption and instrumental parameters such as injection volume.
A metabolic pathway for the prodrug nabumetone to the pharmacologically active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA) by non-cytochrome P450 enzymes
Published in Xenobiotica, 2020
Kaori Matsumoto, Tetsuya Hasegawa, Kosuke Ohara, Chihiro Takei, Tomoyo Kamei, Junichi Koyanagi, Tamiko Takahashi, Masayuki Akimoto
The incubation mixture in 50 mM potassium phosphate buffer (pH 7.4) contained 0.5 mg protein/mL pooled human liver microsomes and S9, a cofactor (NAD+, NADP+, NADH, or NADPH; 1 mM), and 200 μM nabumetone. The preliminary test was performed at a substrate concentration of 10–300 μM in the mixture with microsomes and each metabolite peak was confirmed to be separated. Finally, the substrate concentration was 200 µM at which aldehyde intermediates could be fully detected. The reaction mixture, at a final volume of 500 μL, was preincubated at 37 °C for 3-min before the reaction was initiated by the addition of enzyme sources. After an incubation period of 60-min, each reaction was terminated by the addition of 100 µL of 10% trichloroacetic acid and 600 µL of acetonitrile containing 2.5–10 µM naproxen as the IS. The mixture was vortex-mixed and centrifuged at 10,000 rpm at 4 °C for 5-min. After removal of the protein by centrifugation, 600 µL of the supernatant was applied to cartridges. Solid phase extraction was performed using Bond Elut Certify II cartridges (200 mg, Varian Harbor City, CA) as reported previously (Matsumoto et al., 2015), which had been conditioned with 5% methanol in water. After adsorption of the sample, the cartridges were washed with 4 mL of water. Analytes were then eluted with 6 mL of n-hexane/AcOEt (1:1), evaporated to dryness at 40 °C under a gentle nitrogen stream, and reconstituted in 600 µL of the mobile phase. After filtration (0.45 μm), the eluate was injected into the high-performance liquid-chromatography (HPLC) system for quantification.
Pharmacokinetic study of methylnaltrexone after single and multiple subcutaneous administrations in healthy Chinese subjects
Published in Xenobiotica, 2018
Dan Zhang, Jing-Yi Ma, Man Yang, Ming Deng, Huichen Liu
An aliquot (50 μL) of plasma was mixed with IS (10 μL), acetonitrile–water (1:1, v/v; 10 μL) and water (930 μL). Solid-phase extraction (SPE) was performed using columns with a primary weak cation-exchange mechanism. The SPE columns (CNWBOND WCX SPE Cartridage, 50 mg) were preconditioned with 1 mL of methanol followed by 2 mL of water. Each sample was loaded onto SPE column at 0.4 mL/min and washed with 1 mL of methanol and 1 mL of water. Analytes were eluted with 1 mL of ammonia water–methanol (9:1, v/v). Eluates were evaporated to dryness under a stream of nitrogen at 40 °C, and residues were reconstituted in 170 μL of acetonitrile–water (1:1, v/v). 6 μL of aliquots were subjected to analysis by LC–MS/MS. Samples with concentrations beyond the upper limit of the standard curves were reanalyzed by sample dilution with blank plasma.