title: Stabilization of zeylenone in rat plasma by the presence of esterase inhibitors and its LC-MS/MS assay for pharmacokinetic study.
abstract: Six esterase inhibitors, namely EDTA·2Na(+), NaF, phenylmethanesulfonyl fluoride, dichlorvos, bis-nitrophenyl phosphate (BNPP) and thenoyltrifluoroacetone, and the mixture of NaF and BNPP, were evaluated for the stabilization of labile benzoate containing zeylenone in rat plasma. The mixture appeared to exhibit the most effectively stabilizing effect with the degraded content of zeylenone decreasing from >60% (in the absence of inhibitors) to <6%. Following the stabilization by the addition of NaF (5 mM) and BNPP (5 mM), the analytes in rat plasma were acidified by formic acid and extracted into ethyl acetate at 0°C. After chromatographic separation, the detection of zeylenone was performed on a 3200 Q-Trap with positive ion electrospray mode, monitoring the ion transition m/z 383.2 → 105.0. The method was validated over the range from 2.68 to 1340 ng/mL with inter- and intra-run precision for the quality control samples being less than 6.8%. The assay accuracy was within 100 ± 7.0%. The validated method was successfully applied to a pharmacokinetic study in rats after the intratracheal administration of zeylenone in free drug or polymeric micellar solutions. The results showed that the pulmonary absorption of zeylenone loaded in micelles was significantly retarded compared with that of free drug solutions.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, 151 Malianwa North Road, Haidian District, Beijing 100193, People's Republic of China.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Wei
authors.forename: Rong
authors.initials: R
authors.lastname: Han
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Quan
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Chang
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Liao
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001565:Benzoates / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003510:Cyclohexanes / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004146:Dioxanes / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004950:Esterases / Q000037:antagonists & inhibitors*; D008297:Male; D009596:Nitrophenols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012969:Sodium Fluoride / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001565:Benzoates; D003510:Cyclohexanes; D004146:Dioxanes; D004791:Enzyme Inhibitors; D009596:Nitrophenols; C516240:zeylenone; C002887:bis(4-nitrophenyl)phosphate; D012969:Sodium Fluoride; D004950:Esterases