Increasing throughput of parallel on-line extraction liquid chromatography/electrospray ionization tandem mass spectrometry system for GLP quantitative bioanalysis in drug development.
An approach is described with turbulent flow on-line extraction liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for GLP quantitative bioanalysis of a drug candidate. Two systems were built in-house with standard laboratory parts and equipments. One system consisted of one gradient HPLC pump, one isocratic pump, one ten-port valve, two turbulent flow columns, one analytical column, one autosampler and one mass spectrometer. Using this system, an injection-to-injection cycle time of 0.8 min was achieved. By adding an additional valve, another analytical column and an isocratic pump, the injection-to-injection cycle time decreased to 0.4 min. Validation results from the two systems showed that precision and accuracy were acceptable for GLP quantitative analyses. The system was utilized to support sample bioanalysis of a drug candidate in a first-time in-human clinical trial.
Hsieh
Showchien
S
GlaxoSmithKline, Inc, Research Triangle Park, NC 27709, USA. showchien.k.hsieh@gsk.com
Tobien
Tom
T
Koch
Kevin
K
Dunn
John
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D019411:Clinical Laboratory Techniques / Q000592:standards; D002986:Clinical Trials as Topic / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000592:standards; D015507:Drugs, Investigational / Q000032:analysis*; D006801:Humans; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D018675:Toxicity Tests
D015507:Drugs, Investigational