Drug stability/instability 7 2.

Question 1

How does postmortem degradation affect interpretation

Answer 1

it can significantly affect the interpretation

Question 2

What can impact the in vitro stability

Answer 2

Chemical and Bacteriological

Question 3

How does time effect the stability

Answer 3

Time between autopsy and final toxicological analysis may be extended
Especially if additional analysis or reanalysis requested
Important to know the impact of storage time on quantitative results
Increase or decrease of drug conc may occur

Question 4

Holmgrens study- stufy of drugs being stored at -20C
dont need to know which one increases and which one decrease

Answer 4

Benzodiazepines,Antidepressants, Analgesics
Hypnotics
Most drugs studied stabled in fluorinated femoral blood after the one year
Seven drugs significant differences noted between the first and second analysis
Decrease in concentrations:
Ethanol, THC, zopiclone, and 7-amino0nitrazepam
Desmethylmianserin and desmethyl sertraline, although the parent drug has no change
Increase in concentrations:
Keto

Question 5

Giorgi and meeker 5 year study on the stability of illicit drugs in blood

Answer 5

Cocaine and benzolyeggnoine
Metham
Results
Cocaine and benzoylecgonine showed
Meth and amphetamine are reasonably stable for up to 5 years
Both did have a decrease [albeit small] over 5 year period, with amphetamine being a little less stable
Amphetamine still detectable at 4 years
PCP demonstrated breakdown over the 5 years

Question 6

What drug is very unstable in blood esp. in PM blood if it havent been presrved properly

Answer 6

Cocaine

Question 7

What drugs are affected by chemical instability

Answer 7

Cocaine
Diltiazem
Morphine
Morphine-3-glucuronide*
Morphine-6-Glu

Question 8

Clardy and rangle evalutation of Phenycyclidine stability

Answer 8

unrefrigeration and lottle changes in concetration.
11 had greater changes than 10%

Question 9

Hughes PCP, meth, and amp in urine

Answer 9

stored at room temp and refridergation
all specimens were within 25% of orginial in 3 mo.
6 moth for meth, amp no significant changes whereas PCP were varaible

Question 10

Grieshaber PCP

Answer 10

1 year no change
2 years 10% decrease
3 years 18% decrease
but no cases fell below LOD

Question 11

Cocaine stability

Answer 11

Stability dependent upon temperature and pH
Buffer pH: 5.0, 7.4, and 10.0
Temp: 4 °C and 25 °C
Buffered solutions only benzoylecgonine formed
Rate of hydrolysis increased with temp and pH
Increased temp
pH trending toward basic pH

Question 12

Stability of Benzo

Answer 12

Stability of five barbiturates and thiopental
blood and liver stored at room temp and 4C 2-3 mo.
greater than 75% of original

Question 13

Moriya and Hashimoto PM stability of cocaine and cocaethylene in rabbits

Answer 13

declined over the study period in order of brain<liver<muscle<blood
cocaine degrade rapidly in blood and liver
cocaine was found in brain and muscle at end of 5 days
stability was dependent upon temperature and pH
buffered soln. only cocaethylene was found

Question 14

Moriya and Hashimoto human case

Answer 14

decomposed homogenates formed ethyl alcohol
no changes in cocaine 4.2-5.2
no cocaethylene was detected
putrefactive bacteria had no ability to produce cocaethylene in the presence of cocaine and endogenous ethyl alcohol.

Question 15

Stability of Cathinones

Answer 15

pH does have effect

Question 16

Stability of NBOMe’s

Answer 16

Room temp was unstable and not detected after 60 days
4C decreased by 20% or more and
20C was stable after 180 days

Question 17

Stability of Diltiazem

Answer 17

Calcium ion antagonist
extensively metabolized and some metab. are pharmacologically active

Question 18

Stability of Heroin

Answer 18

Heroin to 6-Am -> morphine
morphine can go to morphine 3/6 glucuronides

Question 19

Stability of Morphine-glucuronides

Answer 19

unconjugated to total morphine ratio stable after more than 1 year storage at room temperature.
Ratios of free to total morphine have been used to evaluate the “acuteness” of the dose
Numerous studies have demonstrated site-dependency of free morphine conc.
Instability of morphine and/or its conjugates shown in some studies could complicate the interpretation of a case

Question 20

Case results for morphine instabilty

Answer 20

Moriya and hashimoto
stable unless in liver where it is hydrolyzed but would not occur at least for a few days in the PM interval
skopp
phot-oxidation of morphine and conjugates may occur in plasma and you might have intenstinal bacterial hydrolysis

Question 21

Bupropion stability

Answer 21

Unstable in plasma but not for major metabolites

Question 22

Propofol instability

Answer 22

No significant changes in propofol conc in plasma under all study parameters
Whole blood propofol conc remained the same over two months when stored at 4 °C, however, became undetectable at 20 days when stored at -20 °C

Question 23

What molecular structures are prone to putrefactive changes

Answer 23

Oxygen bonded to nitrogen as in nitro groups
sulfur:part of a heterocyclic ring
Amino-phenols structures
esters

Question 24

Toluene

Answer 24

Frequently present in cases involving volatile solvents
Saker et al looked at toluene
Quite unstable
Less than 25% loss in first week and two week 16-45% loss
Seven weeks 40-50% loss at higher conc.
After 45+ months
90-95% loss at RT and 83-91% @4C evap.

Question 25

Why do you see changes in morphine concentration

Answer 25

oxidation, bacteria activity

Question 26

Bacteriological instabilty

Answer 26

Bacteria involved in postmortem metabolism of drugs originate in GI tract
(e. coli, bacillus spp.)
Transmigrate from oral cavity, lungs, and GI tract — penetrate intestinal wall entering into blood and lymph systems, then through the body

Nitrobenzodiazepines – very, very unstable in blood samples
Breakdown as soon as five hours after death