Simultaneous gas chromatographic-mass spectrometric determination of dopamine, norsalsolinol and salsolinol enantiomers in brain samples of a large human collective.
Using a solid-phase extraction procedure, an enantioselective derivatization and a gas chromatographic-mass spectrometric method, the levels of dopamine (DA) and of the dopamine-derived tetrahydroisoquinoline alkaloids (R)/(S)-salsolinol (SAL) and norsalsolinol (NorSAL) were determined in human brain samples. A complex pre-analytical synthesis of reference substances as well as deuterated internal standards allowed the standardized and reproducible analysis. In this study, to our best knowledge for the first time, the regional distribution of (R)-SAL and (S)-SAL, as well as NorSAL is examined systematically in a large collective of human brain samples obtained by autopsy. The material comprises 91 brains and 8 standardized specimens in each case. Anatomical concentration differences and no ubiquitous occurence were encountered. Significant amounts of (R)-SAL, (S)-SAL and NorSAL were only found in dopamine-rich areas of the basal ganglia, whereas in other regions of the brain no tetrahydroisoquinolines were detected. These findings suggest that the concentration of the substrate dopamine may determine the alkaloid level during in vivo formation. In our opinion, non-enzymatic formation of SAL via the Pictet-Spengler reaction reveals both the SAL enantiomers. An additional enzymatic synthesis of only (R)-SAL could explain the predominant occurrence of this enantiomer. Especially in the nucleus caudatus, the concentrations of DA, SAL and NorSAL decreased significantly with rising age, which may be consistent with apoptotic effects of ageing. Our data can serve as reference for other studies in humans concerning the etiology of alcoholism or other neurodegenerative diseases with the involvement of tetrahydroisoquinolines.
Musshoff
F
F
Institute of Legal Medicine, Rheinische Friedrich-Wilhelms-University, Stiftsplatz 12, 53111 Bonn, Germany. f.musshoff@uni-bonn.de
Lachenmeier
D W
DW
Kroener
L
L
Schmidt
P
P
Dettmeyer
R
R
Madea
B
B
D000328:Adult; D000367:Age Factors; D000435:Alcoholic Intoxication / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002421:Caudate Nucleus / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D003903:Deuterium / Q000737:chemistry; D004298:Dopamine / Q000032:analysis* / Q000737:chemistry; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D007031:Hypothalamus / Q000737:chemistry; D007546:Isoquinolines / Q000032:analysis* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D009714:Nucleus Accumbens / Q000737:chemistry; D011180:Postmortem Changes; D011699:Putamen / Q000737:chemistry; D015203:Reproducibility of Results; D012490:Salsoline Alkaloids / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry; D012737:Sex Factors; D013237:Stereoisomerism; D017557:Ventral Tegmental Area / Q000378:metabolism
D007546:Isoquinolines; D012490:Salsoline Alkaloids; C036617:salsolinol; C020784:norsalsolinol; D003903:Deuterium; D004298:Dopamine