Unexpected Metabolites and Endogenous Compounds

Question 1

Unexpected metabolites and endogenous cmpds

Answer 1

IPA
GHB
Cocaethylene
Ethylphenidate
Carbon monoxide
Benzodiazepines
Salicylic acid

Question 2

Isopropyl alcohol

Answer 2

Identification of IPA-related deaths challenging
PM detection may be a result of:
Ingestion [purposeful or accidental], Antemortem production, Postmortem production, Postmortem contamination, Cornea recovery,Embalming artifact

Question 3

IPA Antemortem production

Answer 3

From Acetone
Diabetic ketoacidosis
Davis confirmed IPA production via the reduction of acetone
Alcoholic ketoacidosis

Question 4

Other physio-pathological conditions causing increased acetone

Answer 4

Infections
Dehydration
Malnutrition
Hypothermia

Question 5

Isopropyl Alcohol and Acetone case study

Answer 5

Alexander et al found postmortem IPA and acetone conc in non-poisoning cases not significantly different from documented cases of IPA poisoning
Jenkins et al observed that IPA conc and IPA/Acetone ratios were lower as compared to findings in true IPA poisoning
Rohrig isn’t completely sure about Jenkins so dont think need

Question 6

GHB

Answer 6

Gamma amino butyric acid (GABA)
Major source of endogenous GHB

Question 7

Sources of GHB

Answer 7

1,4-Butanediol
Breakdown product from some fatty acids
Formed from putrescine (decomp product)
Seiler (1980) demonstrated GABA formation from putrescine in visceral organs and in CNS of invertebrates
Snead et al (1982) found GHB conc increased by 80-100% in rat brains after intracerebroventricular administration of putrescine

Question 8

Therapeutic uses of GHB

Answer 8

IV anesthetic agent
Tx sleep disorder
Tx alcohol withdrawal syndrome and dependence
Tx opiate withdrawl syndrome

Question 9

Illicit Uses of GHB

Answer 9

Drug abuse
Drug-facilitated crimes

Question 10

GHB formed de novo

Answer 10

Postmortem
In-vitro: container dependent

Question 11

How can you get GHB

Answer 11

endogenous production or exogenous ingestion

Question 12

GC/MS methods for ID and GHB

Answer 12

Many involve the silylation of GHB with SIM or full-scan analysis

Question 13

what is similar to GHB

Answer 13

di-TMS-urea and di-TMS-GHB share common ions and similar chromatographic characteristics
derivatized
trimethyl silyoxate

Question 14

What controls do you need for GHB

Answer 14

Urea
Urea + GHB

Question 15

Therapeutic conc. of GHB

Answer 15

“therapeutic” 50 – 250 mg/L
Lethal > 250mg/L
Xyrem [Na Oxybate]
US FDA approval
Tx of cataplexy associated with narcolepsy

Question 16

Studies from therapeutic conc.

Answer 16

Kerrigan urine 0-7mg/L
LeBeau urine 0-6.63mg/L
Elliot Blood 4-15mg/L
Marinetti blood HB(Heart blood) [119mg/L]
FB [90&97mg/L

Question 17

Interpretation to the studies

Answer 17

Urine/vitreous 10mg/L
Blood Ante-10mg/L
Blood Post 50mg

Question 18

Huntington’s chorea disease

Answer 18

Limited evidence to suggest patients with Huntington’s chorea disease will have elevated conc of GHB
Data limited to brain tissue
No blood, urine, or CSF available
High level of GHB in Huntington’s disease may be related to the decrease in succinate: oxidoreductase (EC 1.3.99.1) activity

Question 19

GHB aciduria

Answer 19

Rare genetic disorder – deficiency in succinic semialdehyde [SSA] dehydrogenase
Altered metabolism of GABA
GABA -> succinic semialdehyde -/> succinate -> kreb’s cycle
Causes of accumulation of GHB