Profiling Neurosteroids in Cerebrospinal Fluids and Plasma by Gas Chromatography/Electron Capture Negative Chemical Ionization Mass Spectrometry

Kim, Yangsuk; Zhang, Hongjian; Kim, Hee‐Yong

doi:10.1006/abio.1999.4384

Cited by 77 publications

(47 citation statements)

References 28 publications

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“…In the case of THP, the LOD/LLOQ reported is the only reference to our knowledge that also includes analytical information about the method (ca. 1 pg/ 10 pg on column [50]) is lower that our LOD/ LLOQ (160/ 400 pg on column (see Table 2)).…”

Section: Discussioncontrasting

confidence: 60%

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A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma

Gachet

Rhyn

Bosch

et al. 2015

Journal of Chromatography B

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Section: Discussioncontrasting

confidence: 60%

“…Different studies have reported levels of THDOC and THP in human and rodent plasma using gas chromatography chemical ionization mass spectrometry (GC-MS) or radioimmunassays [50][51][52][53][54][55]. Using our LC-MS/MS, we were unable to detect these analytes.…”

Section: Discussionmentioning

confidence: 72%

A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma

Gachet

Rhyn

Bosch

et al. 2015

Journal of Chromatography B

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“…Allopregnanolone and related neurosteroids have been commonly analyzed by sensitive radioimmunoassay, gas chromatography, and mass spectrometry assays (Purdy et al, 1990;Bicikova et al, 1995;Griffiths et al, 1999;Chatman et al, 1999;Kim et al, 2000). Many studies describe derivatization for the trace analysis of neurosteroids by mass spectrometry (Cheney et al, 1995;Lierre et al, 2000;Higashi et al, 2005).…”

Section: Analysis Of Neurosteroidsmentioning

confidence: 99%

“…Moreover, liquid phase extraction followed by mass spectrometry with a short run time is the most specific and accurate method for the analysis of 3α-hydroxy neurosteroids in human and rat plasma (Cheney et al, 1995;Ramu et al, 2001). Steroids have been commonly analyzed using liquidliquid extraction and either ECNCI-LC/MS/MS or APCI-LC/MS/MS modes (Griffiths et al, 1999;Kim et al, 2000;Kobayashi et al, 1993;Fredline et al, 1997;Vallee et al, 2000). Influence of eluent composition on ionization efficiency has been extensively studied (Volmer and Hui, 1997).…”

Section: Analysis Of Neurosteroidsmentioning

confidence: 99%

“…Moreover, the possible interference from the 3β-hydroxy isomer of 3α-androstanediol can be resolved by differences in polarity in the HPLC separation, which could be further improved using a longer column and a more gentle gradient so as to achieve better separation of the peaks. The assay sensitivity can be further increased to picomole level by additional procedures such as use of trimethyl-silyl or 2-nitro-4-trifluoromethylphenyl derivatives with negative-ion GC-MS (Kim et al, 2000;Vallee et al, 2000) or LC-MS (Higashi et al, 2005).…”

Section: Advantages and Limitations Of 3α-androstanediol Assaymentioning

confidence: 99%

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Mass spectrometric assay and physiological–pharmacological activity of androgenic neurosteroids

Reddy¹

2008

Neurochemistry International

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Steroid hormones play a key role in the pathophysiology of several brain disorders. Testosterone modulates neuronal excitability, but the underlying mechanisms are obscure. There is emerging evidence that testosterone-derived "androgenic neurosteroids", 3α-androstanediol and 17β-estradiol, mediate the testosterone effects on neural excitability and seizure susceptibility. Testosterone undergoes metabolism to neurosteroids via two distinct pathways. Aromatization of the A-ring converts testosterone into 17β-estradiol. Reduction of testosterone by 5α-reductase generates 5α-dihydrotestosterone, which is then converted to 3α-androstanediol, a powerful GABA A receptormodulating neurosteroid with anticonvulsant properties. Although the 3α-androstanediol is an emerging neurosteroid in the brain, there is no specific and sensitive assay for determination of 3α-androstanediol in biological samples. This article describes the development and validation of mass spectrometric assay of 3α-androstanediol, and the molecular mechanisms underlying the testosterone modulation of seizure susceptibility. A liquid chromatography-tandem mass spectrometry assay to measure 3α-androstanediol is validated with excellent linearity, specificity, sensitivity, and reproducibility. Testosterone modulation of seizure susceptibility is demonstrated to occur through its conversion to neurosteroids with "anticonvulsant" and "proconvulsant" actions and hence the net effect of testosterone on neural excitability and seizure activity depends on the levels of distinct testosterone metabolites. The proconvulsant effect of testosterone is associated with increases in plasma 17β-estradiol concentrations. The 5α-reduced metabolites of testosterone, 5α-dihydrotestosterone and 3α-androstanediol, had powerful anticonvulsant activity. Overall, the testosterone-derived neurosteroids 3α-androstanediol and 17β-estradiol could contribute to the net cellular actions of testosterone in the brain. Because 3α-androstanediol is a potent positive allosteric modulator of GABA A receptors, it could serve as an endogenous neuromodulator of neuronal excitability in men. The 3α-androstanediol assay is an important tool in this area because of the growing interest in the potential to use adjuvant aromatase inhibitor therapy to improve treatment of epilepsy.

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Monoamines and Neurosteroids in Sexual Function During Induced Hypogonadism in Healthy Men

Bloch¹,

Rubinow²,

Berlin³

et al. 2006

Arch Gen Psychiatry

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Profiling Neurosteroids in Cerebrospinal Fluids and Plasma by Gas Chromatography/Electron Capture Negative Chemical Ionization Mass Spectrometry

Cited by 77 publications

References 28 publications

A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma

A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma

Mass spectrometric assay and physiological–pharmacological activity of androgenic neurosteroids

Monoamines and Neurosteroids in Sexual Function During Induced Hypogonadism in Healthy Men

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