title: A rapid and sensitive method for determination of veliparib (ABT-888), in human plasma, bone marrow cells and supernatant by using LC/MS/MS.
abstract: A rapid and sensitive method was developed and validated using a liquid chromatographic method with tandem mass spectrometry detection (LC/MS/MS) for determination of veliparib (ABT-888) in plasma, bone marrow supernatant, and bone marrow cells. Sample preparation involved a single protein precipitation step by the addition of the sample with acetonitrile. Separation of veliparib and the internal standard, A620223.69, was achieved on a Atlantis dC(18) column (100mmx2.1mm, 3microm) column using a mobile phase consisting of acetonitrile-ammonium acetate (2mM) containing formic acid (0.1%, v/v) using isocratic flow at 0.2mL/min for 3min. The analyte and internal standard were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the range of 5-1000nM. The values for both within day and between day precision and accuracy were well within the generally accepted criteria for analytical methods. This method was subsequently used to measure concentrations of veliparib in cancer patients receiving an oral daily dose of 10mg with demonstration of drug accumulation in the marrow compartment and in the target leukemia bone marrow cells.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Reinhardt
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Aleksander
authors.initials: A
authors.lastname: Mnatsakanyan
authors.forename: Linping
authors.initials: L
authors.lastname: Xu
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Ricklis
authors.forename: Alice
authors.initials: A
authors.lastname: Chen
authors.forename: Judith E
authors.initials: JE
authors.lastname: Karp
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Rudek
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001854:Bone Marrow Cells / Q000378:metabolism*; D002138:Calibration; D002458:Cell Fractionation; D011232:Chemical Precipitation; D002853:Chromatography, Liquid / Q000592:standards; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D015588:Observer Variation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D000097:Acetonitriles; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C521013:veliparib; C032159:acetonitrile