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- W1977013079 abstract "Abstract ZT‐1 has been developed as a novel acetylcholinesterase inhibitor, but is rapidly degraded to huperzine A (Hup A) in water or aqueous organic solvents. A sensitive method has been developed for simultaneous determination of ZT‐1 and its active metabolite Hup A in blood, and was applied to the investigation of the pharmacokinetics of ZT‐1 in rats. The method involves immediate hydrogenation of ZT‐1 with sodium borohydride to the stable form rZT‐1 following blood sampling. The NaBH 4 ‐treated blood sample is then submitted to liquid‐liquid extraction, and the resultant extract is analyzed by liquid chromatography with electrospray ionization and tandem mass spectrometry. Huperzine B is used as internal standard for the quantification. ZT‐1 was found to be rapidly absorbed in the intestinal tract, with a time to reach the peak blood concentration ( T peak ) of 5 min after an intragastric dose of ZT‐1 embedded in povidone to rats at 0.5 mg ZT‐1/kg. The mean maximum blood concentration ( C max ) and area under the blood level‐time curve ( AUC 0 → 8 ) of ZT‐1 were 1.57 ng/mL and 0.48 ng · h/mL, respectively. The T peak , C max , and AUC values of the metabolite Hup A were 0.22 h, 109.9 ng/mL, and 96.3 ng · h/mL, respectively. Following an intravenous dose of 0.1 mg ZT‐1/kg rat body weight, the blood concentration of ZT‐1 was higher than that of Hup A, and the AUC 0 → 8 values were 26.2 ng · h/mL for ZT‐1 and 6.0 ng · h/mL for Hup A. The elimination half‐lives ( T 1/2 ) of ZT‐1 and Hup A were 0.68 and 1.47 h, respectively. The oral bioavailability ( F ) of intact ZT‐1 in rats treated with ZT‐1 embedded in povidone was very low, 0.37%. Copyright © 2004 John Wiley & Sons, Ltd." @default.
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- W1977013079 date "2004-02-17" @default.
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- W1977013079 title "A sensitive method for the determination of the novel cholinesterase inhibitor ZT-1 and its active metabolite huperzine A in rat blood using liquid chromatography/tandem mass spectrometry" @default.
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- W1977013079 doi "https://doi.org/10.1002/rcm.1384" @default.
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