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KMID : 0369820090390050321
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Jorunal of Korean Pharmaceutical Sciences
2009 Volume.39 No. 5 p.321 ~ p.325
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Determination of 5-HT agonist KKHQ80114 and KKHQ80109 in Rat Plasma and Urine by Gas-Chromatography/Mass Spectrometry
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Im Hye-Yeon
Kwon Oh-Seung
Park Hye-Sil
Choo Hyun-Ah
Pae Ae-Nim
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Abstract
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5-HT receptors have been considered as therapeutic targets for the treatment of various central nervous system disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. We chemically synthesized KKHQ80114 (K14) and KKHQ80109 (K09), selective 5-HT agonists, with the purpose of developing therapeutic agents for the treatment of obesity. The objective of this work is to investigate analytical methods of these compounds in the plasma and urine of rats by gas chromatography/mass spectrometry. In this experiment, K14 was determined in plasma and urine by using K09 as internal standard. Calibration curves give a good linearity in plasma (r=0.9993) and urine (r=0.9988). Among hexane, ethyl acetate and diethyl ether, the highest peak was observed in diethyl ether. However, ethyl acetate was used since more interfering peaks were observed with diethyl ether. Inter-day precision and accuracy were determined in the ranges of 50-500 ng/mL for plasma and 10-500 ng/ml for urine. Quantitation limits were 50 ng/mL plasma and 25 ng/ mL urine. These data may be applicable for further studies of these compounds including absorption and metabolism due to no pharmacokinetic or analytical data available.
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KEYWORD
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KKHQ80114, KKHQ80109, Gas chromatography/mass selective detector, Plasma, Urine, Rats
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