Trace Determination of Steroids Causing Age-Related Diseases Using LC/MS Combined with Detection-Oriented Derivatization
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概要
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With the rapid shift to an aging society in Japan, age-related diseases, such as osteoporosis, dementia and cancer, are sharply increasing. The measurement of steroids related to these diseases in biological fluids and tissues is useful for elucidation of the nature, diagnosis and treatment of such diseases. LC/MS is considered to be the most promising method for this purpose due to its specificity and versatility, but it sometimes does not demonstrate the required sensitivity for trace amounts of steroids, because steroids have a rather low response using either electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI). To overcome this problem, the author developed detection-oriented derivatization procedures for steroids in LC/MS. For ESI-MS, introduction of a permanently charged moiety is effective. Based on this, 2-hydrazino-1-methylpyridine was developed and used in monitoring prostatic 5α-dihydrotestosterone, a good index for the follow-up of patients affected by prostate cancer under androgen deprivation therapy and salivary dehydroepiandrosterone, which is now often designated as an anti-aging hormone. A proton-affinitive Cookson-type reagent, 4-[2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalyl) ethyl]-1,2,4-triazoline-3,5-dione, was used for the determination of 1α-hydroxyvitamin D_3 [1α(OH)D_3], a synthetic prodrug of the active form of vitamin D_3, in human plasma, and this new LC/positive-APCI-MS method enabled the pharmacokinetic study of 1α(OH)D_3 in humans. Electron-capture APCI-MS based on derivatization with 2-nitro-4-trifluoromethylphenylhydrazine was used for the analysis of neurosteroids, which affect brain excitability through action at the neurotransmitter receptors. With this method, the stress-induced rapid biosynthesis of pregnane-type neurosteroids in rat brains was demonstrated.
- 公益社団法人日本薬学会の論文
- 2006-11-01
著者
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Higashi Tatsuya
Division Of Pharmaceutical Sciences Graduate School Of Natural Science And Technology Kanazawa Unive
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Higashi Tatsuya
Division Of Pharmaceutical Sciences Graduate School Of Natural Science And Technology Kanazawa Unive
関連論文
- Studies on Neurosteroids XXV. Influence of a 5α-Reductase Inhibitor, Finasteride, on Rat Brain Neurosteroid Levels and Metabolism(Analytical Biochemistry)
- Studies on Neurosteroids XXI : An Improved Liquid Chromatography-Tandem Mass Spectrometric Method for Determination of 5α-Androstane-3α,17β-diol in Rat Brains
- Alternative Procedure for Charged Derivatization to Enhance Detection Responses of Steroids in Electrospray Ionization-MS
- Studies on Neurosteroids XVI. Levels of Pregnenolone Sulfate in Rat Brains Determined by Enzyme-linked Immunosorbent Assay Not Requiring Solvolysis
- Simultaneous determination of salivary testosterone and dehydroepiandrosterone using LC-MS/MS: Method development and evaluation of applicability for diagnosis and medication for late-onset hypogonadism
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- Determination of salivary dehydroepiandrosterone using liquid chromatography-tandem mass spectrometry combined with charged derivatization
- Studies on neurosteroids XIX Development and validation of liquid chromatography-tandem mass spectrometric method for determination of 5α-reduced pregnane-type neurosteroids in rat brain and serum
- 2-Hydrazino-1-methylpyridine : a highly sensitive derivatization reagent for oxosteroids in liquid chromatography-electrospray ionization-mass spectrometry
- Trace Determination of Steroids Causing Age-Related Diseases Using LC/MS Combined with Detection-Oriented Derivatization
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