Simultaneous quantification of 2′,3′,5′-tri-O-acetyl-N6-(3-hydroxylaniline)adenosine and its principal metabolites in hamster blood by LC-MS/MS and its application in pharmacokinetics study

被引：4

作者：

Jia, Yufei ^{[1
,2
]}

Wang, Baolian ^{[1
,2
]}

Wu, Xiangmeng ^{[1
,2
]}

Li, Sheng ^{[1
,2
]}

Hu, Jinping ^{[1
,2
]}

Wang, Dongmei ^{[2
,3
]}

Zhu, Haibo ^{[2
,4
,5
]}

Li, Yan ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Inst Mat Med,Dept Drug Metab,State Key Lab Bioact, Beijing Key Lab Nonclin Drug Metab & PK PD Study, Key Lab Act Subst Discovery & Drug Abil Evaluat, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

[3] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Dept Synthet Med Chem,Beijing Key Lab New Drug Me, Beijing 100050, Peoples R China

[4] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing Key Lab New Drug Mech & Pharmacol Evaluat, Beijing 100050, Peoples R China

[5] Chinese Acad Med Sci, Inst Mat Med, Key Lab Biosynthesis Nat Prod, Minist Hlth,Dept Pharmacol, Beijing 100050, Peoples R China

来源：

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2016年 / 1022卷

关键词：

O2; O3; O5; '-Tri-acetyl-N6-(3-hydroxylaniline)adenosine; Metabolites; Quantification; LC-MS/MS; Pharmacokinetics; ACTIVATED PROTEIN-KINASE; AMPK ACTIVATOR;

D O I：

10.1016/j.jchromb.2016.04.004

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

2',3',5'-Tri-O-acetyl-N6-(3-hydroxylaniline)adenosine (IMM-H007, once called WS070117) is being developed as a novel anti-hyperlipidemia agent for its high efficacy and low toxicity. In this study, a sensitive and specific liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was established for the simultaneous quantification of IMM-H007 and its two major metabolites (3S,4R,5R)-2-(hydroxymethyl)-5-(6-((3-hydroxyphenyl)amino)-9H-purin-9-yl)tetrandrofuran-3,4-diol (M-1) and ((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-((3-hydroxyphenyl)amino)-9H-purin-9- yl)tetrahydrofuran-2-yl)methyl dihydrogen phosphate (M-P) in hamster blood. An analogue of IMM-H007, WS070119 was used as the internal standard. Blood samples were prepared by a simple protein precipitation with acetonitrile. The chromatographic separation was performed on a ReproSil-Pur 120C(18) column (3 mu m, 2 mm x 100 mm) with a gradient mobile phase of methanol/water containing 0.1% formic acid (v/v) in a flow rate of 0.2 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) in positive ion selective reaction monitoring (SRM) mode. The monitored transitions were 486.2 -> 4228.1 for IMM-H007, 360.0 -> 3228.0 for M-1, 440.0 -> 228.0 for M-P and 374.1 -> 242.0 for the internal standard, respectively. Satisfactory linearity was obtained for the analytes over the range of 1-500 ng/mL for IMM-H007, 2-1000 ng/mL for M-1 and 10-5000 ng/mL for M-P. The lower limits of the quantification (LLOQs) were 1 ng/mL for IMM-H007, 2 ng/mL for M-1 and 10 ng/mL for M-P. The intra-day and inter-day precisions (RSD, %) of the analytes were within 14.2%, and the accuracy (RE, %) ranged from -9.4% to 10.7%. The average recoveries of the analytes were more than 80.0%. The analytes were proved to be stable during given storage, preparation, and analytic procedures. The method was successfully applied to the pharmacokinetic study in hamsters after oral administration of IMM-H007. (C) 2016 Elsevier B.V. All rights reserved.

引用

页码：46 / 53

页数：8

共 16 条

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