Salsolinol (6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoneline;SAL) is a natural derivative of dopamine. It has been reported that alcohol consumption increases the level of SAL. While R-SAL is formed from enzymatic condensation of dopamine with pyruvic acid, non-enzymatic condensation of dopamine with acetaldehyde, the oxidation product of ethanol, generates the racemic mixture of (R,S)-SAL in vivo. To test a possibility of SAL representing a marker for alcohol addiction, a reliable method for quantification of the (S)-SAL stereo isomer from biological matrices is being established. The previously reported method employed the GC/MS analysis after isolation by solid phase extraction and derivatization by silylation of hydroxyl groups and acylation of the secondary amine with a chiral reagent (R)-2-phenylbutyryl chloride. Upon examining the sensitivity and reproducibility of the method, we found that this approach suffers from drawbacks including poor recovery and stereoisomer conversion during the analysis process, preventing the reliable determination of the S isomer. To improve the sensitivity and stability of the SAL stereoisomer analysis, a new approach using pentafluorobenzyl (PFB) derivatization is being explored. By optimizing derivatization procedures, SAL was derivatized fully at both hydroxyl groups and the secondary amine and analyzed by LC/MS using atmospheric pressure chemical ionization or by GC/MS using electron capture negative ion chemical ionization technique. The resolution of the stereoisomers as well as the sensitivity of the technique with both approaches is being evaluated.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000500-01
Application #
6983196
Study Section
(MS)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code