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Determination, stability and distribution of the abused inhalant 1,1,-difluoroethane

Posted on:2011-12-10Degree:Ph.DType:Dissertation
University:St. John's University (New York), School of PharmacyCandidate:Avella, JosephFull Text:PDF
GTID:1444390002964534Subject:Health Sciences
Abstract/Summary:
1,1-difluoroethane (DFE) is a halogenated hydrocarbon propellant used for dusting electronic equipment. When inhaled, DFE causes intoxication and loss of muscular coordination. This paper describes a method for the quantitation of DFE, examines its stability in biological specimens and investigates DFE toxicokinetics. DFE quantitation used a gas chromatography headspace technique that employed solventless calibrators. Two curves using 0.5 mL blood calibrators ranging from A: 0.225-1.350 to B: 9.0-180.0 mg/L were developed. Linearity was 0.9992 and 0.9995, LOD = 0.018, LOQ = 0.099 (C.V 9.92%) and ULOL = 27,000.0 mg/L.;A study examining the effect of storage on DFE concentration in blood and urine was conducted that characterized concentration changes in DFE enriched specimens over 3 months. DFE levels dropped in a manner dependant upon headspace and temperature (blood r2 = 0.9781 and urine r2 = 0.9768). At 4°C, loss from blood was -95.4% and -99.2% from urine but was prevented by maintaining sample seal integrity. Samples in vacuum tubes and frozen headspace vials were unchanged. The partition coefficient (lambda) of DFE in blood at 37°C (lambda37) was 1.766 and lambda 4 = 3.02. The urine/gas partition coefficient at 37°C was determined to = 1.03 and lambda4 = 2.85.;To examine DFE toxicokinetics, groups (n=3) of Sprague-Dawley rats were exposed to 30 seconds of 20 L/min DFE and the uptake, distribution and elimination in different body compartments was examined. Intoxication was evident within 20 sec and lasted until approximately 8 min. Tissue collection was performed at timed intervals (0, 10, 20, 30, 45, 60, 120, 240, & 480, 900 sec) and specimens were analyzed for DFE content. Plots of concentration (log) vs. time were consistent with a two compartment model. Blood and brain levels were initially 352 and 519 mg/L or kg respectively. After 8 min no signs of impairment were apparent and DFE levels had dropped to 10.0 and 6.5 in blood and brain. Total uptake was 4% of the administered dose. The half life (t½) DFE during beta slope elimination was 86, 110 and 168 seconds in blood, brain and heart.
Keywords/Search Tags:DFE, Blood
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