1993 Fiscal Year Final Research Report Summary
ISOTOPIC FRACTIONATION OF DEUTERATED DRUGS AND APPLICATION FOR TRACER STUDY.
| Project/Area Number |
04671335
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | FUKUYAMA UNIVERSITY |
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Principal Investigator |
GOROMARU Tsuyoshi FUKUYAMA UNIVERSITY, FACULTY OF PHARMACY & PHARMACEUTICAL SCIENCES PROFESSOR, 薬学部, 教授 (80037605)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Deuterium label / Capillary-GC / Isotopic fractionation / Isotope dilution analysis |
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| Research Abstract |
Isotopic fractionation of drugs from thier deuterated analogues were examined by gas chromatography using capillary column. Seven kinds of deuterated isopropylantipyrine (IPA) l-phenyl-d_5.2-methyl-d_3, 3-methyl-d_3, 4-isopropyl-d_6, 2-methyl-3-methyl-d_6, l-phenyl-3-methyl-d_8 and 3-methyl-4-isopropyl-d_9, were synthesized to determine the separation conditions. The separation of IPA and deuterated IPAs were proportion to the number of labeled deuterium atoms and iversely to the temperature of GC column oven. These phenomena were also boserved in the case of propofol (PF), fentanyl (FT) and aminopyrine (AM).
The present isotopic fractionation procedure were applied to the isotope dilution analysis of IPA, PF, FT and AM.By the measurement of the samples prepared .by the addition of known amount of drug (H ; IPA, PF, FT or AM) and its deuterated analogue (D ; IPA-d_9, PF-d_6, FT-d_<19> or AM-d_9) to the control plasma or serum, linear relationship between peak area ratio (H/D) and added amount ratio (H/D) were observed with good reproducibility. The high sensitive detection of AM and FT were achieved at Pg-ng/ml level with using a surface ionization detector. Furthermore, the present method were applied to determine the plasma level of AM in rat for evaluation of hepatic function, and to determine the serum level of FT in surgical patients for pharmacokinetic analysis of FT.
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