A rapid ultra HPLC-MS/MS method for the quantitation and pharmacokinetic analysis of 3-deazaneplanocin A in mice.
3-Deazaneplanocin A (DZNep) has been shown to have anti-cancer activity in numerous cancer types and its continued preclinical, and eventual clinical, drug development will require rapid and sensitive bioanalytical methods in order to quantitate this drug for pharmacokinetic analyses. The ultra HPLC with positive thermospray tandem mass spectrometric (LC-MS/MS) detection affords the most sensitive (limit of quantitation 5ng/mL) and rapid (3min run time) bioanalytical method to date for DZNep. Due to the polar nature of this drug and the internal standard (tubercidin), a hydrophilic-interaction column (HILIC) was used. The method was accurate, with less than 10% deviation from nominal values, as well as precise, where both within-day and between-day precisions were less than 15%. A liquid-liquid extraction procedure was able to recover ∼90% of drug from a small volume (50μL) of mouse plasma. This method was successfully applied to a pharmacokinetic study in mice intravenously injected with DZNep.
Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, USA.
Cody J
CJ
Peer
Mahadev
M
Rao
Shawn D
SD
Spencer
Shandiz
S
Shahbazi
Patricia S
PS
Steeg
David S
DS
Schrump
William D
WD
Figg
D000241:Adenosine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D016018:Least-Squares Analysis; D059625:Liquid-Liquid Extraction; D051379:Mice; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014372:Tubercidin / Q000097:blood / Q000737:chemistry
C048460:3-deazaneplanocin; D000241:Adenosine; D014372:Tubercidin