| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
It is well known that many compounds are accumulated in hair. Thus, the hair analysis provides one important means for determining individual past history of long-term chemical exposure. In spite of many papers regarding hair analysis, the studies of drug disposition in the hair root are very rare, because it is believed that the permeation of drugs into the hair from circulated blood is very slow. However, recent research has shown that administered drugs are relatively promptly incorporated into the hair shaft via the hair roots. The results suggest the possibility of drug monitoring in hair roots shortly after drug administration, similar to drug monitoring using blood.
In the present studies, bioactive compounds such as drugs and biogenic amines were determined by HPLC coupled with electrospray ionization-mass spectrometry (ESI-MS). The proposed procedure was applied to the determination in hair shaft of Dark Agouti rats after intraperitoneal (i.p.) administration of benzodiazepines
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(triazolam, alprazolam, estazolam and midazolam). Various metabolites accompanied with parent drugs were identified in the hair shaft. The time course studies of parent drugs and the metabolites in both hair root and plasma were also carried out after single i.p. administration of benzodiazepines. The results suggested that the concentrations of parent drugs and the metabolites in the hair samples were mainly dependent upon those in the plasma.
Consequently, investigation of the fate of a drug in the hair roots and a comparison with that in the plasma seem to be important in order to elucidate drug disposition in hair and interpret the retrospective drug exposure.
Sensitive determination of histamine (HA) in hair was also carried out by column-switching HPLC-ESI-MS. HA was labeled with excess amounts of DBD-F at 60℃ for 30 min in a basic medium. The proposed method was applied to HA determination in the hair of Dark Agouti rats and healthy volunteers. The determination of HA in the plasma of rats and humans was also successfully performed by this method. Because the proposed method provides good precision and trace detection of HA in hair, the analytical technique seems to be applicable for the determination of various biogenic amines in hair. Less
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