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 5alpha-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 1alpha-hydroxyvitamin D3 [1alpha(
OH)D3], a synthetic
prodrug of the active form of
vitamin D3, in human plasma, and this new LC/positive-APCI-MS method enabled the pharmacokinetic study of 1alpha(
OH)D3 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.