Transcript GLUTETHIMIDE

GLUTETHIMIDE
PREPARED BY
ABEER ALSANOOSI
INTRODUCTION
*Glutethimide is a hypnotic sedative that was introduced in 1954 as a safe alternative to
barbiturates to treat insomnia.
*Before long, however, it had become clear that glutethimide was just as likely to cause
addiction and caused similarly severe withdrawal symptoms.
*It was originally a Schedule III drug in the United States under the Controlled
Substances Act, but in 1991 it was upgraded to Schedule II more than a decade after
recreational abusers discovered that combining the drug with codeine produced a
euphoria which closely resembles that obtained from heroin.
*The street name for a combination of two doriden and four Codeine and a "load" or
"doors and fours" .
*Glutethimide is a Schedule II drug under the Convention on Psychotropic
Substances[1]. Doriden is the brand-name version of the drug, which is rarely
prescribed today
MEDICAL USE
*Used as an hypnotic in insomnia but rarely as a
sedative
* glutethimide was initially believed to be almost
free from side effects. However, further
experience of its toxicity and because its
dependence liability glutethimide has been
banned in many countries and many companies
have stopped production.
SIDE EFFECT
*Less common
Skin rash, Blurred vision; clumsiness or unsteadiness;
confusion; dizziness; hangover effect; headache;
nausea; vomiting
*Rare
Sore throat and fever; unusual bleeding or bruising; •
unusual excitement; unusual tiredness or weakness
*More common
Drowsiness (daytime)
SIDE EFFECT
*Symptoms of overdose
Bluish coloration of skin; confusion (continuing);
convulsions (seizures); fever; low body
muscle ;memory problems; temperature,
spasms or twitching; shortness of breath or slow
or troubled breathing; slow heartbeat; slowness
or loss of reflexes; slurred speech; staggering;
trembling; trouble in concentrating.
ANALYSIS
1)UV spectrophotometry :
*gives rather more specificity.
*Dissolve a portion of material in ethanol to achieve an appropriate instrument
response. If necessary, centrifuge or filter the mixture and analyse the clear
at 252 nm, 258 nm supernatant. The spectrum in ethanol gives deltamax
(A| = 18) and 264 nm.
*Glutethimide is unstable at alkaline pH, due to hydrolysis of the glutarimide
ring. Adjustment of the pH to >11 (e.g. by addition of 4M NaOH or
ammonium hydroxide) to the ethanolic solution of glutethimide results in a
characteristic decline in absorbance at 230 - 235 nm over a time period of
some 20 minutes
ANALYSIS
2)Thin layer chromatography:
*is highly appropriate for identification of glutethimide, and may be either an inhouse system or a commercially-available system such as Toxi-Lab.
*The material can be dissolved in an organic solvent such as methanol or
dichloromethane and applied directly to the plate. Using silica plates without
modifiers and standard systems, the Rf of glutethimide is 0.75 on methanol /
concentrated ammonia (100: 1.2), and 0.62 on ethyl acetate / methanol /
ammonia (85:15:6).
*Several locating reagents can be used. Mercurous nitrate reagent is the most
specific, and gives a dark grey response with a sensitivity of approximately 10
ng. However, the purple response produced by mercuric chloridediphenylcarbazone reagent, and the positive reaction to Dragendorff or
.)acidified iodoplatinate are also useful but are less characteristic).
ANALYSIS
3)Gas chromatography :
*can be used after dissolving the material in a small amount of
organic solvent (e.g. 10 mg in 10 mL methanol).
*The Retention index for glutethimide is 1836 on OV1, SE30,
DB5 or similar phases. Isothermal analysis may be performed
at about 220°C, without the need for derivatization. Flame
ionization detection gives adequate sensitivity (2 to 5 ng on
column), and nitrogen-phosphorus detection gives additional
selectivity .
*Mass spectrometry can be applied to the gas chromatographic
identification of glutethimide in suspect materials.
ANALYSIS
4)HPLC:
*may be used to identify glutethimide, and most published methods involve
reverse phase chromatography with UV detection.
*Kabra et al. (1978) used a C18 column with a mobile phase of acetonitrile /
phosphate buffer (300 µL 1M KH2PO4 and 50 µL 0.9 M phosphoric acid
in 1800 mL water) [215:785].
*Using isocratic elution at 50°C glutethimide was detected at 195 nm with a
relative retention of 0.55 to the internal standard methylphenytoin.
* Glutethimide was detected at 208 nm with a relative retention of 1.57 to the
internal standard tolylphenobarbital. Additional confirmation of identity may
be obtained by performing a full scan analysis on the appropriate portion of
the HPLC effluent.
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