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العنوان
Chemical and toxicological Studies of thiopental compound /
المؤلف
Othman, Fatma Ismail.
هيئة الاعداد
باحث / فاطمةإسماعيل عثمان
مشرف / إي?ت عبدالسيد إسحق
مناقش / غادة فؤاد أحمد
مناقش / إي?ت عبدالسيد إسحق
تاريخ النشر
2013.
عدد الصفحات
114 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
Analytical Chemistry
تاريخ الإجازة
1/1/2013
مكان الإجازة
جامعة بنها - كلية العلوم - Chemistry
الفهرس
Only 14 pages are availabe for public view

from 135

from 135

Abstract

General anesthesia depresses the CNS and cause loss of consciousness associated with an inability to perceive pain. An ideal anesthetic would produce unconsciousness analgesia, and muscle relaxation suitable for all surgical procedures and would be metabolically inert and rapidly eliminated. No anesthetic fulfils all there requirements in safe concentrations and it is customary to employ a number of drugs to achieve the required conditions while minimizing the risk of toxicity. (Martindale, 1999).
Although all types of anesthesia involve some risk major side effects, complications occur; the role of forensic toxicologist to detect and determine the drugs used in the anesthesia and quantifies it for the malpractice claims cases. (Brendan, 2007). Among anesthesia drugs thiopental was chosen for this study as an example of drugs used in general anesthesia.
The development of modern forensic chemical examinations is directly related to the development of scientific fundamentals or methodological approaches to examining material evidence, which is most frequent in criminal investigations.
The present day forensic expert examination can not be performed without reliable, highly sensitive, and selective chemical and physical techniques.
Various versions of chromatographic analysis are among there techniques widely used in forensic expert examinations. (Fitsev et al., 2004).
Colorimetric and chromatographic analysis in combination with other techniques, such as optical spectroscopy (UV and IR) which provide an opportunity to determine unambiguously the structure of the studied drug(thiopental) to identify, determine concentrations and to reveal the identity and differences in the composition of the trace components in test materials. Our study aims to develop a simple, rapid and accurate method to extract and clean thiopental and its major metabolite pentobarbital in rich fat. A quantitative determination of thiopental by means of a gas chromatography equipped with mass spectrometer was attempted.
The present work is an attempt to:
І) Employ the different toxicological analytical procedures (spot tests), TLC, UV spectrophotometry and GC to reveal which of these methods or all together more suitable for the identification and differentiation of the studied drug, thiopental.
П) Estimation the postmortem drug concentration in some tissues of rat injected different doses of the drug.
The results obtained can be summarized as follow:
• Color tests revealed that some chemical reagents are suitable for the identification of thiopental and pentobarbital as follow:-
• Orange color with ferric reagent was produced only with thiopental and green color was produced with Zwikker due to the presence of sulfur, while pentobarbital gave pink color which is the typical color obtained with the barbiturate class and this is due to the presence of C=O and NH are adjacent in a ring of imides, Clark (2004).
• On the other hand, no colors were obtained by thiopental and pentobarbital drug with Beam’s, concentrated sulfuric acid, FPN, furfural, Liebermann’s, PDA, , sodium hydroxide, Vitali- Morrineand Chen- Kao. Thus these reagents are not suitable to identify the studied drug.
• Different coloring reagents were sprayed on the chromatoplates of TLC and the results revealed that:
• Koppanyi- Zwikker reagent may be considered as specific to identify and differentiate the studied drugs, since it produced a characteristic and specific color with thiopental and pentobarbital.
• Palladium chloride can be considered as specific for identifying thiopental and pentobarbital as it gives yellow color and white color with thiopental and pentobarbital, respectively.
• It is of much interest to notice that iodoplatinate, give a white color with thiopental only.
• The chromatographic behavior of the drug thiopental and its metabolite on silica gel (GF254) is considered very important for the identification. Therefore different elueting solvents were used and Rf values were calculated. e.g Cyclohexane: Acetone: Chloroform (70 : 25: 5) (Rf =0.64 and 0.58 for thiopental and pentobarbital, respectively), petroleum ether: acetone (40:10) (Rf =0.51 and 0.76 for thiopental and pentobarbital, respectively). Isopropyl alcohol: chloroform: ammonia (90:90:4)( Rf =0.75 and 0.86 for thiopental and pentobarbital, respectively),which proved that these eluents are suitable for identification of the drug and its metabolite.
• The UV spectrum of thiopental and pentobarbital showed absorption band at λ max 258 nm and λ max 287 nm, respectively.
• Mass spectrum of sodium thiopental shows molecular ion peaks m/z= [264-Na]. + and base peak at 29 .
While pentobarbital shows [M+] at m/z =[226].+, and base
peak at 141.
• IR spectrum of thiopental and pentobarbital demonstrated the characteristic function groups of both drugs. Thiopental showed bands at 1730-1680cm-1due to υ C =O and at 1540 cm-1due υ C=,S and at 3300 -3500cm-1due to υ NH.
IR spectrum of pentobarbital showed bands a 1760,1960 cm-1due to υ C=O and at3300 -3500cm-1due to υ NH.
• The quantitative estimations of the drugs in different organs of rats by GC/MS were successfully carried out. Calibration curve was plotted using different concentrations from thiopental and pentobarbital against the area under peaks, and consequently the concentrations of drug residue in different tissues and blood were obtained.
• The distribution of thiopental and pentobarbital in different organs of rats, using different doses as well as their abundance per gram tissue was illustrated. The data showed that the higher concentration of the drug and its metabolite at the brain.
• Thiopental administration intraperitoenally with single two doses. The animals were sacrificed after three hours and showed nearly the same tissue organs descending order in both doses (1/5 and 1/10 LD50).. Brain, kidney and liver showed the higher of thiopental concentration than muscle, spleen; blood and hair with no dose dependency.