Analytical Artifacts Day 3 part 1

Question 1

Standard impurities

Answer 1

Deuterated Internal standards

Structure analog impurity
Method development should eliminate these

Question 2

Deuterated Internal Standard

Answer 2

best because closest in structure to target cmpd

(the cmpd may be 99% pure)
Native drug is the impurity

Question 3

Pharmaceutical Impurties
Meth need to know

Answer 3

Morphine
Heroin marker 6AM low levels in pharmaceutical grade
Amphetamine
Trace amts of methamphetamine
Imipramine: Desipramine and iminodibenzyl
Desipramine:Imipramine and iminodibenzyl
ephedrine to methamphetamine
small methamphetamine to amp

Question 4

Analytical process induced changes

Answer 4

Volatility during dry down process
Extraction
Injector port

Question 5

Volatility during dry down process
What can be affected

Answer 5

Meth/amp
Phencyclidine
Fenfluramine
ALkylated Barbiturates

Question 6

Extraction to reduce volatility of drugs

Answer 6

Addition of 1% methanolic HCL reduce volatility of drugs
Soln. may become oxidizing exposed to light and air
Avoid; soln <4 weeks and store in brown bottles

Question 7

Analytical Artifacts

Answer 7

standard
analytical process
laboratory

Question 8

Extraction Methadone, Amitriptyline, and codeine

Answer 8

Decrease up to 35%
No identifiable decomp products

Question 9

extraction Chlorpromazine

Answer 9

Highly variable recovery:5-70% loss
Evidence suggest conversation to sulphoxide [metab]

Question 10

Extraction Phenylbutazone and oxyphenbutazone. not common

Answer 10

degradation under acidic extraction conditions and heat induced loss of oxy

Question 11

Injector port

Answer 11

breakdown and conversion

Question 12

Injector port breakdown

Answer 12

Methylnaltrexone to oxymorphone
Formation inlet thermolysis or side rxn w/deriv agent
Possible acetylation of morphine to 6-AM
Co-ingestion of ASA

Production of EDDP metabolite >180C
ephedrine to methamphetamine

Question 13

Injector port conversion

Answer 13

Promethazine/Chlorpromazine formation
On column reduction of sulpoxide metab
Methadone

Question 14

Extraction Conversion

Answer 14

Acid and heat
conversion of CBD to THC
Diazepam Metab.

Question 15

Benzo

Answer 15

reductive enzymatic formation
B-glucuronidase employed to deconjugate glucuronides in urine drug testing source of artifact product
oxazepam-glucuronide and oxazepam reduced to nordiazepam

Question 16

Reductive transformation of 3-Hydrobenzodiazepam

Answer 16

conversion of lorazepam to delorazepam during enzymatic hydrolysis

Question 17

Normeperidine ethyl carbamate in vivo formation of drug not common

Answer 17

normeperidine is analyzed in biological specimens and the extract is ultimately concentrated in chloroform

Question 18

Study of Normeperidine

Answer 18

Pirl et al made similar observation with the extraction of desipramine

Question 19

Laborotry contamination

Answer 19

General and process carry over

Question 20

General

Answer 20

Glassware (class A), reusable measuring devices/syringe

Question 21

Process carry-over

Answer 21

sample proceeded by high concentration sample
autosamplers