| Project/Area Number |
10670391
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KUDO Keiko Kyushu Univ., Graduate Sch. Med. Sci., Lecturer, 大学院・医学系研究科, 講師 (10186405)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Naoki Kyushu Univ., Graduate Sch. Med. Sci., Assistant, 大学院・医学系研究科, 助手 (10315088)
TSUJI Akiko Kyushu Univ., Graduate Sch. Med. Sci., Assistant, 大学院・医学系研究科, 助手 (10171993)
IKEDA Noriaki Kyushu Univ., Graduate Sch. Med. Sci., Professor, 大学院・医学系研究科, 教授 (60176097)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Time of drug exposure / Triazolam / α -hydroxytriazolam / 4-hydroxytriazolam / Tetracaine / GC-MS / p-butylaminobenzoic acid |
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| Research Abstract |
In order to diagnose the time of drug exposure from concentrations of original drug and its metabolites in human samples, we first tried to establish the sensitive method to determine original drug and its metabolites simultaneously in triazolam and tetracaine.
Triazolam and its major metabolites, α -hydroxytriazolam and 4-hydroxytriazolam were effectively extracted using 3-step solvent extraction procedure followed by tert-butyldimethylsilyl derivatization, and subjected to CG-MS in the negative ion chemical ionization mode. Estazolam was served as internal standard. The calibration curve for each compound was linear in the range from 0.5 to 100 ng/g, and the lower limit of detection was 0.1 ng/g for whole blood and 0.2 ng/g for urine. Tetracaine and its metabolite, p-butylaminobenzoic acid, in the tissues were successfully extracted by a liquid-liquid extraction procedure, and analyzed by CG-MS as free base for tetracaine and as tert-butyldimethylsilyl derivative for the metabolite. Dibucaine and p-dimethylaminobenzoic acid were used as internal standards. The calibration curve for each compound was linear in the range from 10 to 1000 ng/0.5g, and the lower limit of detection was 10ng/g for tetracaine and 0.6 ng/g for the metabolite.
A preliminary study was carried out by analyzing concentrations of triazolam and its metabolites in human urine collected every 2 hours from a volunteer who took 1 tablet of triazolam (0.25 mg). α -hydroxytriazolam was found to be excreted to urine faster than 4-hydroxytriazolam, thus the possibility of determining the time of exposure of triazolam by using the concentration ratio of α -hydroxytriazolam to 4-hydroxytriazolam was suggested.
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