title: Automated 96-well liquid-liquid back extraction liquid chromatography-tandem mass spectrometry method for the determination of ABT-202 in human plasma.
abstract: A high-throughput bioanalytical method using automated sample transferring, automated liquid-liquid back extraction and liquid chromatography-tandem mass spectrometry was developed in a GLP regulated environment for the determination of ABT-202 in human plasma. Samples of 0.30 ml were transferred into 96-well plate using an automatic liquid handler. Automated liquid-liquid extraction (LLE) was carried out on a 96-channel programmable liquid handling workstation using methyl tert-butyl ether as the extraction solvent. A dual-HPLC with single mass spectrometer configuration was utilized to provide a reliable and routine means to increase sample throughput. The standard curve range was 0.38-95.02 ng/ml. There was no interference from endogenous components in the blank plasma tested. The accuracy (% bias) at the lower limit of quantitation (LLOQ) was 7.7% and the precision (% CV) for samples at the LLOQ was 4.7%. The inter-day % CV and % bias of the quality control samples were < or = 6.8 and < or = 7.6%, respectively. Coefficients of determination, a measure of linearity, ranged from 0.994 to 0.997. The method was accurate and reproducible and was successfully applied to generate plasma concentration-time profiles for human subjects after low oral doses of the compound.
authors.affiliation: Abbott Laboratories, Department of Clinical Drug Analysis, Dept. R46W, Bldg. AP13A-2, 100 Abbott Park Road, Abbott Park, IL 60064-6126, USA. naxing.r.xu@abbott.com
authors.forename: Naxing
authors.initials: N
authors.lastname: Xu
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kim
authors.forename: Hope
authors.initials: H
authors.lastname: Gregg
authors.forename: Azza
authors.initials: A
authors.lastname: Wagdy
authors.forename: Brendan A
authors.initials: BA
authors.lastname: Swaine
authors.forename: Min S
authors.initials: MS
authors.lastname: Chang
authors.forename: Tawakol A
authors.initials: TA
authors.lastname: El-Shourbagy
mesh_terms: D000284:Administration, Oral; D001331:Automation; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D009538:Nicotine / Q000097:blood; D018722:Nicotinic Agonists / Q000097:blood* / Q000493:pharmacokinetics; D011725:Pyridines / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013048:Specimen Handling
chemical_list: C496017:ABT-202; D018722:Nicotinic Agonists; D011725:Pyridines; D009538:Nicotine