title: Study on the bioavailability of nateglinide-hydroxypropyl-beta-cyclodextrin complex capsule in rabbits by liquid chromatographic-tandem mass spectrometry.
abstract: To evaluate the bioavailability of nateglinide-hydroxypropyl-beta-cyclodextrin (HPCD) complex, a rapid and specific liquid chromatographic-tandem mass spectrometric method was developed and validated to determine nateglinide in rabbit serum. The analyte was extracted from serum samples by liquid-liquid extraction, separated on a Zorbax C(18) column and detected by tandem mass spectrometry with an atmospheric pressure chemical ionization interface. Daidzein was used as the internal standard. The method has a lower limit of quantitation of 0.25 mg/L using 200 micro L serum. The intra- and inter-day relative standard deviations calculated from quality control (QC) samples were below 4%. The inter-day relative error was within 1%. Nateglinide serum concentrations in rabbits given nateglinide-hydroxypropyl-beta-cyclodextrin complex were much higher than those given the free drug. Significant difference was observed in main pharmacokinetic parameters of t(max) and C(max) but not AUC(0-t) between the complex and free drug. It was concluded that the absorption rate of nateglinide-HPCD complex was enhanced, compared with that of nateglinide free drug.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.forename: Dafang
authors.initials: D
authors.lastname: Zhong
authors.forename: Chunshun
authors.initials: C
authors.lastname: Zhao
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.forename: Ruhua
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid / Q000379:methods*; D003510:Cyclohexanes / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011786:Quality Control; D011817:Rabbits; D012680:Sensitivity and Specificity; D047392:beta-Cyclodextrins / Q000493:pharmacokinetics*
chemical_list: D002214:Capsules; D003510:Cyclohexanes; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000077715:Nateglinide; D010649:Phenylalanine