title: Quantitative and qualitative analysis of the novel antitumor 1,3,4-oxadiazole derivative (GLB) and its metabolites using HPLC-UV and UPLC-QTOF-MS.
abstract: Fructose-based 3-acetyl-2,3-dihydro-1,3,4-oxadiazole (GLB) is a novel antitumor agent and belongs to glycosylated spiro-heterocyclic oxadiazole scaffold derivative. This research first reported a simple, specific, sensitive and stable high performance liquid chromatography-ultraviolet detector (HPLC-UV) method for the quantitative determination of GLB in plasma. In this method, the chromatographic separation was achieved with a reversed phase C18 column. The calibration curve for GLB was linear at 300 nm. The lower limit of quantification was 10 ng/mL. The precision, accuracy and stability of the method were validated adequately. This method was successfully applied to the pharmacokinetic study in rats for detection of GLB after oral administration. Moreover, the structures of parent compound GLB and its two major metabolites M1 and M2 were identified in plasma using an ultra performance liquid chromatography-electrospray ionization-quadrupole-time of flight- mass spectrometry (UPLC-ESI-QTOF-MS) method. Our results indicated that the di-hydroxylation (M1) and hydroxylation (M2) of GLB are the major metabolites. In conclusion, the present study provided valuable information on an analytical method for the determination of GLB and its metabolites in rats, can be used to support further developing of this antitumor agent.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, PR. China.
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, PR. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory of Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, PR China.
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Meng
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR. China.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Li
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR. China.
authors.forename: Zhong-Jun
authors.initials: ZJ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, PR. China.
authors.forename: Ying-Yuan
authors.initials: YY
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, PR. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, PR. China.
authors.forename: Ya-Qing
authors.initials: YQ
authors.lastname: Lou
authors.affiliation: Millennium Pharmaceuticals-Takeda, Cambridge, Massachusetts, USA.
authors.forename: Chuang
authors.initials: C
authors.lastname: Lu
authors.affiliation: Laboratory of Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, PR China.
authors.forename: Gui-Fang
authors.initials: GF
authors.lastname: Dou
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, PR. China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D006207:Half-Life; D006900:Hydroxylation; D008297:Male; D010069:Oxadiazoles / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D010069:Oxadiazoles; C583463:1,3,4-oxadiazole