Approaches to higher-throughput pharmacokinetics (HTPK) in drug discovery.

With pressure on pharmaceutical companies to reduce time-to-market and improve the success rate of new drug candidates, higher-throughput pharmacokinetic (HTPK) support has become an integral part of many drug discovery programmes. This report details the amalgamation of robotics, new sample preparation technologies and highly sensitive and selective mass spectrometric detection systems to deliver the promise of HTPK. A historical perspective on automated bioanalysis with the current approaches and future prospects for the discipline are described.

[1]  C. M. Jones,et al.  Use of reduced sorbent bed and disk membrane solid-phase extraction for the analysis of pharmaceutical compounds in biological fluids, with applications in the 96-well format. , 1997, Journal of chromatography. B, Biomedical sciences and applications.

[2]  Rodrigues Ad,et al.  Preclinical drug metabolism in the age of high-throughput screening: an industrial perspective. , 1997 .

[3]  M H Tarbit,et al.  High-throughput approaches for evaluating absorption, distribution, metabolism and excretion properties of lead compounds. , 1998, Current opinion in chemical biology.

[4]  S. P. Fodor,et al.  Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. , 1994, Journal of medicinal chemistry.

[5]  S. Pleasance,et al.  The Use of Automated Solid Phase Extraction in the '96 well' Format for High Throughput Bioanalysis using Liquid Chromatography Coupled to Tandem Mass Spectrometry , 1996 .

[6]  Clauwaert,et al.  Investigation of the quantitative properties of the quadrupole orthogonal acceleration time-of-flight mass spectrometer with electrospray ionisation using 3,4-methylenedioxymethamphetamine , 1999, Rapid communications in mass spectrometry : RCM.

[7]  D K Walker,et al.  Automated 96-well solid phase extraction for the determination of doramectin in cattle plasma. , 1998, Journal of pharmaceutical and biomedical analysis.

[8]  B. Matuszewski,et al.  Matrix effect in quantitative LC/MS/MS analyses of biological fluids: a method for determination of finasteride in human plasma at picogram per milliliter concentrations. , 1998, Analytical chemistry.

[9]  K Kronkvist,et al.  Automated sample preparation for the determination of budesonide in plasma samples by liquid chromatography and tandem mass spectrometry. , 1998, Journal of chromatography. A.

[10]  T. Olah,et al.  Determination of L-365,260, a new cholecystokinin receptor (CCK-B) antagonist, in plasma by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry. , 1992, Biological mass spectrometry.

[11]  Giles,et al.  High throughput liquid chromatography/mass spectrometric analyses using a novel multiplexed electrospray interface. , 1999, Rapid communications in mass spectrometry : RCM.

[12]  B. Matuszewski,et al.  Development of high-performance liquid chromatography-tandem mass spectrometric methods for the determination of a new oxytocin receptor antagonist (L-368,899) extracted from human plasma and urine: a case of lack of specificity due to the presence of metabolites. , 1998, Journal of chromatography. B, Biomedical sciences and applications.

[13]  E. Woolf,et al.  Effect of the sample matrix on the determination of indinavir in human urine by HPLC with turbo ion spray tandem mass spectrometric detection. , 1998, Journal of pharmaceutical and biomedical analysis.

[14]  S. P. Fodor,et al.  Applications of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions. , 1994, Journal of medicinal chemistry.

[15]  D. Wu,et al.  High throughput liquid chromatography/mass spectrometry bioanalysis using 96-well disk solid phase extraction plate for the sample preparation. , 1998, Rapid communications in mass spectrometry : RCM.

[16]  F. Beaudry,et al.  In vivo pharmacokinetic screening in cassette dosing experiments; the use of on-line Pprospekt liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry technology in drug discovery. , 1998, Rapid communications in mass spectrometry : RCM.

[17]  M. Hedenmo,et al.  On-line solid-phase extraction with automated cartridge exchange for liquid chromatographic determination of lipophilic antioxidants in plasma. , 1994, Journal of chromatography. A.

[18]  J. Henion,et al.  Liquid-liquid extraction in the 96-well plate format with SRM LC/MS quantitative determination of methotrexate and its major metabolite in human plasma. , 1999, Analytical chemistry.

[19]  T. Olah,et al.  The effects of sample preparation methods on the variability of the electrospray ionization response for model drug compounds. , 1999, Rapid communications in mass spectrometry : RCM.

[20]  U. Timm,et al.  Concept and specification of LIMS for pharmacokinetic studies , 1996 .

[21]  T. Olah,et al.  A direct technique for the simultaneous determination of 10 drug candidates in plasma by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry interfaced to a Prospekt solid-phase extraction system. , 1997, Journal of pharmaceutical and biomedical analysis.

[22]  R. Plumb,et al.  The use of turbulent flow chromatography/mass spectrometry for the rapid, direct analysis of a novel pharmaceutical compound in plasma. , 1997, Rapid communications in mass spectrometry : RCM.

[23]  J. Henion,et al.  Peer Reviewed: Sample Preparation for LC/MS/MS: Analyzing Biological and Environmental Samples , 1998 .

[24]  D L Buhrman,et al.  Quantitation of SR 27417 in human plasma using electrospray liquid chromatography-tandem mass spectrometry: A study of ion suppression , 1996, Journal of the American Society for Mass Spectrometry.

[25]  T. Olah,et al.  Determination of L-654,066, a new 5 alpha-reductase inhibitor in plasma by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry. , 1992, Biological mass spectrometry.

[26]  J J Burbaum,et al.  New technologies for high-throughput screening. , 1997, Current opinion in chemical biology.

[27]  P. Woollard,et al.  Cassette dosing: rapid in vivo assessment of pharmacokinetics , 1998 .

[28]  J. Broach,et al.  High-throughput screening for drug discovery. , 1996, Nature.

[29]  M. Kriška,et al.  Automatic solid-phase extraction and high-performance liquid chromatographic determination of quinidine in plasma. , 1994, Journal of chromatography. A.

[30]  S. Walker,et al.  Pharmaceutical innovation by the seven UK-owned pharmaceutical companies (1964-1985). , 1988, British journal of clinical pharmacology.

[31]  M K Bayliss,et al.  High-throughput pharmacokinetics: cassette dosing. , 1999, Current opinion in drug discovery & development.

[32]  R. Plumb,et al.  Optimisation and routine use of generic ultra-high flow-rate liquid chromatography with mass spectrometric detection for the direct on-line analysis of pharmaceuticals in plasma. , 1998, Journal of chromatography. A.

[33]  Richard P. Schneider,et al.  Robotics for the bioanalytical laboratory A flexible system for the analysis of drugs in biological fluids , 1987 .

[34]  U. Neue,et al.  Straightforward solid-phase extraction method for the determination of verapamil and its metabolite in plasma in a 96-well extraction plate. , 1998, Journal of chromatography. A.

[35]  Walter A. Korfmacher,et al.  Novel in vivo procedure for rapid pharmacokinetic screening of discovery compounds in rats , 1999 .

[36]  J. Kehler,et al.  Determination of Pranlukast and its metabolites in human plasma by LC/MS/MS with PROSPEKT on-line solid-phase extraction. , 1998, Journal of mass spectrometry : JMS.

[37]  S. Fischer,et al.  Signal enhancement for gradient reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry analysis with trifluoroacetic and other strong acid modifiers by postcolumn addition of propionic acid and isopropanol , 1995, Journal of the American Society for Mass Spectrometry.

[38]  T. Twomey,et al.  Liquid chromatographic analysis of doxazosin in human serum with manual and robotic sample preparation. , 1988, Journal of chromatographic science.

[39]  Yuan-Qing Xia,et al.  The need for adequate chromatographic separation in the quantitative determination of drugs in biological samples by high performance liquid chromatography with tandem mass spectrometry , 1999 .