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  • 1
    ISSN: 1432-0738
    Keywords: Key words Physiologically based model  ;   C(±)P(±)-soman  ;  Stereoisomers  ;  Toxicokinetics  ;   Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A physiologically based model was developed which describes the in vivo toxicokinetics of the highly reactive nerve agent C(±)P(±)-soman at doses corresponding to 0.8–6 LD50 in the atropinized guinea pig. The model differentiates between the summated highly toxic C(±)P(−)-soman stereoisomers at supralethal doses and the individual nontoxic C(±)P(+)-isomers. Several toxicant-specific parameters for the soman stereoisomers were measured in guinea pig tissue homogenates. Cardiac output and blood flow distribution were measured in the atropinized, anesthetized, and artificially ventilated guinea pig. The model was validated by comparison of the time courses for the blood concentrations of the two pairs of stereoisomers in the guinea pig after i.v. bolus administration with the blood concentrations predicted by the model. The predictions put forward for the summated C(±)P(−)-isomers are in reasonable agreement with the experimental data obtained after doses corresponding to 2 and 6 LD50. In view of large differences in the rates of hydrolysis of the C(±)P(+)-isomers, these two isomers had to be differentiated for satisfactory modeling of both isomers. In order to model the toxicokinetics of C(±)P(−)-soman at a dose of 0.8 LD50, the almost instantaneous elimination of the C(+)P(−)-isomer at that dose had to be taken into account. The sensitivity of the predictions of the model to variations in the parameters has been studied with incremental sensitivity analysis. The results of this analysis indicate that extension to a model involving four individual stereoisomers is desirable in view of large differences in the biochemical characteristics of the two C(±)P(−)- and C(±)P(+)-isomers.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0935-6304
    Keywords: Micropacked liquid chromatography ; Enantiomer separation ; HPLC-TID ; Organophosphorus pesticides ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Microcolumn liquid chromatography (micro-LC) of some chiral organophosphorus pesticides has been studied using Chiralcel OD columns and simultaneous ultraviolet (UV) and phosphorus selective detection, the latter by means of a micro-UV cell coupled on-line to a thermionic detector (TID). Micro-LC showed a ca. 5-fold improved separation impedance, a ca. 1.8-fold increased column permeability, and greater inertness compared with conventional LC.By using the TID, organophosphorus pesticides could be satisfactorily determined at trace levels, the detection limit being 4 pg/s of phosphorus. The response of the micro-LC-TID system is linear in the range of 0.05-20 ng (r = 0.9994).
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 22 (1999), S. 153-158 
    ISSN: 0935-6304
    Keywords: Vapor analysis ; nerve agents ; sulfur mustard ; data acquisition ; automation ; valve injection ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: ---A method is presented for the continuous analysis of generated vapors of the nerve agents soman and sarin and the blistering agent sulfur mustard. By using a gas sampling valve and a very short (15 cm) column connected to an on-column injector with a “standard length” column, the system can either be calibrated or used for performing high speed gas analyses. When using a flame ionization detector, the detection limit was ca. 100 ppb (ca. 0.5-1.0 mg/m3). This technique is applied in inhalation toxicokinetic studies of nerve agents and mustard gas in the guinea pig.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 17 (1994), S. 95-97 
    ISSN: 0935-6304
    Keywords: Chemical warfare agents ; Microcolumn liquid chromatography ; Enantiomeric separation ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An improved interface for the on-line coupling of microcolumn liquid chromatography (micro-LC) with thermionic detection (TID) is described. Modifications have been made to enable separate adjustment of the eluent introduction and the detector flame temperature in order to improve the sensitivity and ease of use of the system.The micro-LC-TID was used for the chiral separation of the nerve agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothioate (VX). Baseline separation for the enantiomers of VX was obtained on Chiralcel OD using 1% isopropanol in hexane as the eluent. The detection limit of VX using 60 nl injections is ca. 5 μg/ml (ppm range). However, when using large-volume injections (10 μl) the detection limit is ca. 25 ng/ml (ppb range).
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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