JOURNAL ARTICLE

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

Yufei Jia, Baolian Wang, Xiangmeng Wu, Sheng Li, Jinping Hu, Dongmei Wang, Haibo Zhu, Yan Li
Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 2016 June 1, 1022: 46-53
27082762
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)tetrahdrofuran-3,4-diol (M1) and ((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-((3-hydroxyphenyl)amino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methyl dihydrogen phosphate (MP) 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 120C18 column (3μm, 2mm×100mm) with a gradient mobile phase of methanol/water containing 0.1% formic acid (v/v) in a flow rate of 0.2mL/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→228.1 for IMM-H007, 360.0→228.0 for M1, 440.0→228.0 for MP and 374.1→242.0 for the internal standard, respectively. Satisfactory linearity was obtained for the analytes over the range of 1-500ng/mL for IMM-H007, 2-1000ng/mL for M1 and 10-5000ng/mL for MP. The lower limits of the quantification (LLOQs) were 1ng/mL for IMM-H007, 2ng/mL for M1 and 10ng/mL for MP. 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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
27082762
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"