A rapid and sensitive method for determination of veliparib (ABT-888), in human plasma, bone marrow cells and supernatant by using LC/MS/MS

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 52; no. 1; pp. 122 - 128
• Main Authors: Reinhardt, Sarah, Zhao, Ming, Mnatsakanyan, Aleksander, Xu, Linping, Ricklis, Rebecca M., Chen, Alice, Karp, Judith E., Rudek, Michelle A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-05-2010; Elsevier
• Subjects: ABT-888; Acetonitriles - chemistry; Administration, Oral; Analysis; Analytical, structural and metabolic biochemistry; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - blood; Antineoplastic Agents - pharmacokinetics; Benzimidazoles - administration & dosage; Benzimidazoles - blood; Benzimidazoles - pharmacokinetics; Biological and medical sciences; Bone Marrow Cells - metabolism; Calibration; Cell Fractionation; Chemical Precipitation; Chromatography, Liquid - standards; Clinical Trials as Topic; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - blood; Enzyme Inhibitors - pharmacokinetics; Fundamental and applied biological sciences. Psychology; General pharmacology; Humans; LC/MS/MS; Medical sciences; Observer Variation; PARP inhibitor; Pharmacokinetics; Pharmacology. Drug treatments; Poly(ADP-ribose) Polymerase Inhibitors; Reference Standards; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization - standards; Tandem Mass Spectrometry - standards; Veliparib; Pharmacokinetics; LC/MS/MS; ABT-888; PARP inhibitor; Veliparib; Human; Biological fluid; Supernatant; HPLC chromatography; Determination; Blood plasma; Osteoarticular system; Rapid technique; Mass spectrometry MS/MS; Bone marrow; Inhibitor; Bone; Quantitative analysis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2009.12.015

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 (100
mm
×
2.1
mm, 3
μm) column using a mobile phase consisting of acetonitrile–ammonium acetate (2
mM) containing formic acid (0.1%, v/v) using isocratic flow at 0.2
mL/min for 3
min. The analyte and internal standard were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the range of 5–1000
nM. 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 10
mg with demonstration of drug accumulation in the marrow compartment and in the target leukemia bone marrow cells.