title: Quantification of 3-deazaneplanocin A, a novel epigenetic anticancer agent, in rat biosamples by hydrophilic interaction liquid chromatography-tandem mass spectrometric detection.
abstract: A sensitive and selective LC-MS/MS based bioanalytical method was developed and validated for the quantification of 3-deazaneplanocin A (DZNep), a novel epigenetic anti-tumor drug candidate, in Sprague-Dawley (SD) rat biosamples (plasma, urine, feces and tissue samples). The method comprises a phenylboronic acid (PBA)-containing solid phase extraction procedure, serving for binding and clean-up of DZNep in rat biosamples spiked with tubercidin (as internal standard). The analytes were separated on an Agilent hydrophilic interaction chromatography (HILIC) column. LC-MS/MS in positive ion mode was used to perform multiple reaction monitoring at m/z of 263/135 and 267/135 for DZNep and tubercidin, respectively. The limit of quantification (LOQ) of DZNep in rat biosamples was 20 ng/mL. The data of intra-day and inter-day accuracy were within 15% of nominal concentration while the precision (relative standard deviation) less than 10% for all biosamples. The extraction recoveries for DZNep and tubercidin were consistent and reproducible (around 80%) and the matrix effects were negligible (around 10% suppression) in all biosamples. This method was demonstrated to be applicable for pharmacokinetic studies of DZNep in SD rats.
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.forename: Jasmine Chiat-Ling
authors.initials: JC
authors.lastname: Ong
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
authors.forename: Eli
authors.initials: E
authors.lastname: Chan
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D002853:Chromatography, Liquid / Q000379:methods*; D004064:Digestive System / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D016018:Least-Squares Analysis; D008168:Lung / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution; D014372:Tubercidin / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; C048460:3-deazaneplanocin; D000241:Adenosine; D014372:Tubercidin