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The Analysis of Neuroactive Steroids by Mass Spectrometry

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

The effects of neuroactive steroids on the nervous system have increasingly become a rewarding topic for neuoscientific investigations. The use of radioimmunoassay in the past has sometimes provided invalid results, such as those reported for pregnenolone sulfate. Therefore, a variety of mass spectroscopic methods have been developed, which incorporate unambiguous criteria of identification. However, since concentrations of these neuroactive steroids in the plasma and central nervous system are normally very low, it is necessary to employ ultrasensitive and specific methodology to measure these compounds in select regions of the brain. The most sensitive method of gas chromatography/mass spectrometry reported thus far is electron captureā€negative chemical ionization/mass spectrometry performed with selective ion monitoring. This allows several related neuroactive steroids and their deuterated internal standards to be measured in the same chromatogram. Such methods and further refinements are under continual development.

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Abbreviations

API/MS:

atmospheric pressure chemical ionization/mass spectrometry

DHEA:

dehydroepiandrosterone

DHEAS:

dehydroepiandrosterone sulfate

ESI:

electrospray ionization

FAB:

fast atom bombardment

FTā€ICR:

Fourier transform ion cyclotron resonance

GC:

gas chromatography

GC/MS:

gas chromatography/mass spectroscopy

GC/ECā€NCI/MS:

gas chromatography/electron captureā€negative chemical ionization/mass spectrometry

HFBA:

heptafluorobutyrate

HPLC:

high performance liquid chromatography

ID:

isotope dilution

LC/MS:

liquid chromatography/mass spectroscopy

MS:

mass spectrometry

MS/MS:

tandem mass mass spectrometry

m/z:

mass/charge ratio

PREG:

pregnenolone

PREGS:

pregnenolone sulfate

RIA:

radioimmunoassay

SIM:

selective ion monitoring

S/N:

signal/noise ratio

TH PROG:

tetrahydroprogesterone

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Acknowledgments

This is publication number 16768ā€NP from The Scripps Research Institute. The research was supported by National Institutes of Health Grants AA06420 and AA07456 from the National Institute on Alcohol Abuse and Alcoholism. We are grateful for the assistance of Elizabeth Gordon and Michael Arends in the preparation of this manuscript.

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Purdy, R.H., Fitzgerald, R.L., Everhart, E.T., Mellon, S.H., Alomary, A.A., Parsons, L.H. (2007). The Analysis of Neuroactive Steroids by Mass Spectrometry. In: Lajtha, A., Baker, G., Dunn, S., Holt, A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30401-4_7

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