Advances in High Throughput Quantitative Drug Discovery Bioanalysis

Integrated Strategies for Drug Discovery Using Mass Spectrometry

Volumn , Issue , 2005, Pages 315-358

  Ackermann, Bradley L ^a   Berna, Michael J ^a   Murphy, Anthony T ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

LC MS technology; Nanotechnology solutions; Quantitative drug discovery bioanalysis

Indexed keywords

EID: 75249094278     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/0471721034.ch11     Document Type: Chapter

References (133)

1. Gilbert, J.D.; Hand, E.L.; Yuan, A.S.; Olah, T.V.; Covey, T.R. "Determination of L-365, 260, a New Cholecystokinin Receptor (CCK-B) Antagonist, in Plasma by Liquid Chromatography/Atmospheric Pressure Chemical Ionization Mass Spectrometry," Biol. Mass Spectrom. 21, 63-68 (1992).
2. Murphy, A.T.; Kasper, S.C.; Gillespie, T.A.; DeLong, A.F. "Determination of Xanomeline and Active Metabolite, N-Desmethylxanomeline, in Human Plasma by Liquid Chromatography-Atmospheric Pressure Chemical Ionization Mass Spectrometry," J. Chromatogr B. Biomed Appl. 668, 273-280 (1995).
3. Lee, M.S.; Kearns, E.H. "LC/MS Applications in Drug Development," Mass Spectrom. Rev. 18, 187-279 (1999).
4. Ackermann, B.L.; Berna, M.J.; Murphy, A.T. "Recent Advances in Use of LC/MS/MS for Quantitative High-Throughput Bioanalytical Support of Drug Discovery," Curr. Top. Med. Chem. 2, 56-66 (2002).
5. Brewer, E.; Henion, J. "Atmospheric Pressure Ionization LC/MS/MS Techniques for Drug Disposition Studies," J. Pharm. Sci. 87, 395-402 (1998).
6. Plumb, R.S.; Dear, G.J.; Mallett, D.N.; Higton, D.M.; Pleasance, S.; Biddlecombe, R.A. "Quantitative Analysis of Pharmaceuticals in Biological Fluids Using High-Performance Liquid Chromatography Coupled to Mass Spectrometry: A Review," Xenobiotica 31, 599-617 (2001).
7. Jemal, M. "High-Throughput Quantitative Bioanalysis by LC/MS/MS," Biomed. Chromatogr. 14, 422-429 (2000).
8. FDA Guidance for Industry. Center for Drug Evaluation and Research. Biopharmaceutics, Bioanalytical Method Validation. Issued 5/2001. http://www.fda. gov/cder/guidance/index.htm
9. Shah, V.P.; Midha, K.K.; Findlay, J.W.; Hill, H.M.; Hulse, J.D.; McGilveray, I.J.; McKay, G.; Miller, K.J.; Patnaik, R.N.; Powell, M.L.; Tonelli, A.; Viswanathan, C.T.; Yacobi, A. "Bioanalytical Method Validation-A Revisit with a Decade of Progress," Pharm. Res. 17, 1551-1557 (2000).
10. Kebarle, P.; Tang, L. "From Ions in Solution to Ions in the Gas Phase: The Mechanism of Electrospray Mass Spectrometry," Anal. Chem. 65, 972A-986A (1993).
11. Enke, C.G. "A Predictive Model for Matrix and Analyte Effects in Electrospray Ionization of Singly-Charged Ionic Analytes," Anal. Chem. 69, 4885-4893 (1997).
12. Bruins, A.P. "Mechanistic Aspects of Electrospray Ionization," J. Chromatogr. A 794, 345-357 (1998).
13. Sunner, J.; Nicol, G.; Kebarle, P. "Factors Determining Relative Sensitivity of Analytes in Positive Mode Atmospheric Pressure Ionization Mass Spectrometry," Anal. Chem. 60, 1300-1307 (1988).
14. Berna, M.; Shugert, R.; Mullen, J. "Quantitative Determination of Olanzapine in Human Plasma and Serum by Liquid Chromatography/Tandem Mass Spectrometry," J. Mass Spectrom. 33, 1003-1008 (1998).
15. Matuszewski, B.K.; Constanzer, M.L.; Chavez-Eng, C.M. "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," Anal. Chem. 70, 882-889 (1998).
16. Schaefer, W.H.; Dixon, F. Jr. "Effect of High-Performance Liquid Chromatography Mobile Phase Components on Sensitivity in Negative Atmospheric Pressure Chemical Ionization Liquid Chromatography-Mass Spectrometry," J. Am. Soc. Mass Spectrom. 7, 1059-1069 (1996).
17. Kuhlmann, F.E.; Apffel, A.; Fischer, S.M.; Goldberg, G.; Goodley, P.C. "Signal Enhancement for Gradient Reverse-Phase High-Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry Analysis with Trifluoroacetic and Other Strong Acid Modifiers by Post-Column Addition of Proprionic Acid with Isopropanol," J. Am. Soc. Mass Spectrom. 6, 1221-1225 (1995).
18. Temesi, D.; Law, B. "The Effect of LC Eluent Composition on MS Responses Using Electrospray Ionization," LC-GC 17, 626-632 (1999).
19. King, R.; Bonfiglio, R.; Fernandez-Metzler, C.; Miller-Stein, C.; Olah, T. "Mechanistic Investigation of Ionization Suppression in Electrospray Ionization," J. Am. Soc. Mass Spectrom. 11, 942-950 (2000).
20. Gallagher, R.T.; Balogh, M.P.; Davey, P.; Jackson, M.R.; Sinclair, I.; Southern, L.J. "Combined Electrospray Ionization-Atmospheric Pressure Chemical Ionization Source for Use in High-Throughput LC-MS Applications," Anal. Chem. 75, 973-977 (2003).
21. Liu, C.C.;Kovarik, P.; LeBlanc, Y.; Sakuma, T.; Garofolo, F.; Marland, A.; Pang, H.; McIntosh, M.; Wong, E.; Kennedy, M.; Covey, T. "Use of Fast Settling De-Solvation Heaters and Rapid Ionization Process Selection for Enhanced LC-MS/MS Performance," in Proceedings of the 50th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, FL, June 2-6, 2002.
22. Siegel, M.M.; Tabei, K.; Tong, H.; Lamber, F.; Candela, L.; Zoltan, B. "Evaluation of a Dual Electrospray Ionization/Atmospheric Pressure Ionization Source at Low Flow Rates (~50 μL/min) for the Analysis of Both Highly and Weakly Polar Compounds," J. Am. Soc. Mass Spectrom. 9, 1196-1203 (1998).
23. Robb, D.B.; Covey, T.R.; Bruins, A.P. "Atmospheric Pressure Photoionization: An Ionization Method for Liquid Chromatography-Mass Spectrometry," Anal. Chem. 72, 3653-3659 (2000).
24. Yang, C.; Henion, J. "Atmospheric Pressure Photoionization Liquid Chromatographic-Mass Spectrometric Determination of Idoxifene and Its Metabolites in Human Plasma," J. Chromatogr. A 13, 155-165 (2002).
25. Doerge, D.R.; Fogle, C.M.; Paule, M.G.; McCullagh, M.; Bajic, S. "Analysis of Methylphenidate and its Metabolite Ritalinic Acid in Monkey Plasma by Liquid Chromatography/Electrospray Ionization Mass Spectrometry," Rapid Commun. Mass Spectrom. 14, 610-623 (2000).
26. Tiller, P.R.; Cunniff, J.; Land, A.P.; Schwartz, J.; Jardine, I.; Wakefield, M.; Lopez, L.; Newton, J.F.; Burton, R.D.; Folk, B.M.; Buhrman, D.L.; Price, P.; Wu, D. "Drug Quantitation on a Benchtop Liquid Chromatography-Tandem Mass Spectrometry System," J. Chromatogr. A. 771, 119-125 (1997).
27. Weiboldt, R.; Campbell, D.A.; Henion, J. "Quantitative Liquid Chromatographic-Tandem Mass Spectrometric Determination of Orlistat in Plasma with a Quadrupole Ion Trap," J. Chromatogr. B. 708, 121-129 (1998).
28. Zhang, N.; Fountain, S.T.; Bi, H.; Rossi, D.T. "Quantification and Rapid Metabolite Identification in Drug Discovery Using API Time-of-Flight LC/MS," Anal. Chem. 72, 800-806 (2000).
29. Clauwaert, K.M.; Van Bocxlaer, J.F.; Major, H.J.; Claereboudt, J.A.; Lambert, W.E.; Van den Eeckhout, E.M.; Van Peteghem, C.H.; De Leenheer, A.P. "Investigation of the Quantitative Properties of the Quadrupole Orthogonal Acceleration Time-of-Flight Mass Spectrometer with Electrospray Ionisation Using 3, 4-Methylenedioxymethamphetamine," Rapid Commun. Mass Spectrom. 13, 1540-1545 (1999).
30. Yang, L.;Wu, N.; Rudewicz, P.J. "Applications of NewLiquid Chromatography-Tandem Mass Spectrometry Technologies for Drug Development Support," J. Chromatogr. A 926, 43-55 (2001).
31. Jemal M.; Ouyang, Z. "Enhanced Resolution Triple-Quadrupole Mass Spectrometry for Fast Quantitative Bioanalysis Using Liquid Chromatography/Tandem Mass Spectrometry: Investigations of Parameters That Affect Ruggedness," Rapid Commun. Mass Spectrom. 17, 24-38 (2003).
32. Yang, L.; Amad, M.; Winnik, W.M.; Schoen, A.E.; Schweingruber, H.; Mylchreest, I.; Rudewicz, P.J. "Investigation of an Enhanced Resolution Triple Quadrupole Mass Spectrometer for High-Throughput Liquid Chromatography/Tandem Mass Spectrometry Assays," Rapid Commun. Mass Spectrom. 16, 2060-2066 (2002).
33. Needham, S.; Jeanville, P.; Cole, M. "The Role of ESI-TOF in Drug Discovery Metabolism," in Proceedings of the 47th ASMS Conference on Mass Spectrometry and Allied Topics, Dallas, TX, June 13-16, 1999.
34. Zhang, H.; Henion, J. "Comparison Between Liquid Chromatography-Timeof-Flight Mass Spectrometry and Selected Reaction Monitoring Liquid Chromatography-Mass Spectrometry for Quantitative Determination of Idoxifene in Human Plasma," J. Chromatogr. B. Biomed. Sci. Appl. 757, 151-159 (2001).
35. Hager, J.W. "A New Linear Ion Trap Mass Spectrometer," Rapid Commun. Mass. Spectrom." 16, 512-526 (2002).
36. Hopfgartner, G.; Husser, C.; Zell, M. "Rapid Screening and Characterization of Drug Metabolites Using a New Quadrupole-Linear Ion Trap Mass Spectrometer," J. Mass Spectrom. 38, 138-150 (2003).
37. Simpson, H.; Berthemy, A.; Buhrman, D.; Burton, R.; Newton, J.; Kealy, M.; Wells, D.; Wu, D. "High Throughput Liquid Chromatography/Mass Spectrometry Bioanalysis Using 96-Well Disk Solid Phase Extraction Plate for Sample Preparation," Rapid Commun. Mass Spectrom. 12, 75-82 (1998).
38. Jemal, M.; Teitz, D.; Ouyang, Z.; Khan, S. "Comparison of Plasma Sample Purification by Manual Liquid-Liquid Extraction, Automated 96-Well Liquid-Liquid Extraction and Automated 96-Well Solid-Phase Extraction for Analysis by High-Performance Liquid Chromatography with Tandem Mass Spectrometry," J. Chromatogr. B Biomed. Sci. Appl. 732, 501-508 (1999).
39. Watt, A.P.; Morrison, D.; Locker, K.L.; Evans, D.G. "Higher Throughput Bioanalysis by Automation of a Protein Precipitation Assay Using 96-Well Format with Detection by LC-MS/MS," Anal. Chem. 72, 979-984 (2000).
40. Mullett, W.M.; Martin, P.; Pawliszyn, J. "In-Tube Molecularly Imprinted Polymer Solid-Phase Microextraction for the Selective Determination of Propranolol," Anal. Chem. 73, 2383-2389 (2001).
41. Rule, G.S.; Henion, J.D. "Determination of Drugs from Urine by On-Line Immunoaffinity Chromatography-High-Performance Liquid Chromatography-Mass Spectrometry," J. Chromatogr. 582, 103-112 (1992).
42. Rule, G.; Henion, J. "A 384-Well Solid-Phase Extraction for LC/MS/MS Determination of Methotrexate and its 7-Hydroxy Metabolite in Human Urine and Plasma," Anal. Chem. 73, 439-443 (2001).
43. Biddlecombe, R.A.; Benevides, C.; Pleasance, S. "A Clinical Trial on a Plate? The Potential of 384-Well Format Solid Phase Extraction for High-Throughput Bioanalysis Using Liquid Chromatography/Tandem Mass Spectrometry," Rapid Commun. Mass Spectrom. 15, 33-40 (2001).
44. Henion, J.; Brewer, E.; Rule, G. "Sample Preparation for LC/MS/MS: Knowing the Basic Requirements and the Big Picture of an LC/MS System can Ensure Success in Most Instances," Anal. Chem. 70, 650A-656A (1998).
45. Ackermann, B.L.; Murphy, A.T.; Berna, M.J. "The Resurgence of Column SwitchingTechniques to Facilitate RapidLC/MS/MSBased Bioanalysis in Drug Discovery," Am. Pharm. Rev. 5, 54-63 (2002).
46. Allanson, J.P.; Biddlecombe, R.A.; Jones, A.E.; Pleasance, S. "The Use of Automated Solid-Phase Extraction in the 96-Well Format for High Throughput Bioanalysis Using Liquid Chromtography Coupled to Tandem Mass Spectrometry," Rapid Commun. Mass Spectrom. 10, 811-816 (1996).
47. Janiszewski, J.; Schneider, R.; Hoffmaster, K.; Swyden, M.; Wells, D.; Fouda, H. "Automated Sample Preparation Using Membrane Microtiter Extraction for Bioanalytical Mass Spectrometry," Rapid Commun. Mass Spectrom. 11, 1033-1037 (1997).
48. Zhang, N.; Hoffman, K.L.; Li, W.; Rossi, D.T. "Semi-Automated 96-Well Liquid-Liquid Extraction for Quantitation of Drugs in Biological Fluids," J. Pharm. Biomed. Anal. 22, 131-138 (2000).
49. Murphy, A.T.; Johnson, J.T.; Ackermann, B.L.; Gillespie, T.A.; Garner, C.O. "Bioavailability of Zyprexa Lead Generation Formulations in Dog Plasma Using LC/MS/MS Detection of Protein Precipitation Supernatants Injected From 96-Well Microtiter Plates," in Proceedings of the 46th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, FL, May 31-June 5, 1998.
50. Biddlecombe, R.A.; Pleasance, S. "Automated Protein Precipitation by Filtration in the 96-Well Format," J. Chromatogr. BBiomed. Sci. Appl. 12, 257-265 (1999).
51. Polson, C.; Sarkar, P.; Incledon, B.; Raguvaran, V.; Grant, R. "Optimization of Protein Precipitation Based upon Effectiveness of Protein Removal and Ionization Effect in Liquid Chromatography-Tandem Mass Spectrometry," J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 785, 263-275 (2003).
52. Kaye, B.; Herron, W.J.; Macrae, P.V.; Robinson, S.; Stopher, D.A.; Venn, R.F.; Wild, W. "Rapid, Solid Phase Extraction Technique for the High-Throughput Assay of Darifenacin in Human Plasma," Anal. Chem. 68, 1658-1660 (1996).
53. Lensmeyer, G.L.; Oroskar, A. "Evaluation Model for Identification of Distinctive Silanol Variations in SPE Sorbents Used for LC-MS/MS Bioanalytical Sample Preparation," in Proceedings of the 50th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, FL, June 2-6, 2002.
54. Wells, D.A.; Lensmeyer, G.L.; Wiebe, D.A. "Particle-Loaded Membranes as an Alternative to Traditional Packed-Column Sorbents for Drug Extraction-In Depth Comparative Study," J. Chromatogr. Sci. 33, 386-392 (1995).
55. Cheng, Y.F.; Neue, U.D.; Bean, L. "Straightforward Solid-Phase Extraction Method for the Determination of Verapamil and its Metabolite in Plasma in a 96-Well Extraction Plate," J. Chromatogr. A 828, 273-281 (1998).
56. Mallet, C.R.; Lu, Z.; Fisk, R.; Mazzeo, J.R.; Neue, U.D. "Performance of an Ultra-Low Elution-Volume 96-Well Plate: Drug Discovery and Development Applications," Rapid Commun. Mass Spectrom. 17, 163-170 (2003).
57. Harvey, M.C.; Stearns, S.D. "HPLC Sample Injection and Column-Switching Using a 10-Port Multifunctional Valve," Am. Lab. 14, 68 (1982).
58. Needham, S.R.; Cole, M.J.; Fouda, H.G. "Direct Plasma Injection for High-Performance Liquid Chromatographic-Mass Spectrometric Quantitation of the Anxiolytic Agent CP-93393," J. Chromatogr. B 718, 87-94 (1998).
59. Schellen, A.; Ooms, B.; van Gils, M.; Halmingh, O.; van der Vlis, E.; van de Lagemaat, D.; Verheij, E. "High Throughput On-Line Solid Phase Extraction/Tandem Mass Spectrometric Determination of Paclitaxel in Human Serum," Rapid Commun. Mass Spectrom. 14, 230-233 (2000).
60. Ackermann, B.L.; Ruterbories, K.J.; Hanssen, B.R.; Lindstrom, T.D. "Increasing the Throughput of Microsomal Stability Screening Using Fast Gradient Elution LC/MS," in Proceedings of the 46th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, FL, May 31-June 5, 1998.
61. McLoughlin, D.A.; Olah, T.V.; Gilbert, J.D. "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," J. Pharm. Biomed. Anal. 15, 1893-1901 (1997).
62. Beaudry, F.; LeBlanc, J.Y.C.; Coutu, M.; Brown, N. "In Vivo Pharmcokinetic Screening in Cassette Dosing Experiments: The Use of On-Line Prospekt Liquid Chromatography/Atmospheric Pressure Chemical Ionization Tandem Mass Spectrometry Technology in Drug Discovery," Rapid Commun. Mass Spectrom. 12, 1216-1222 (1998).
63. Gao, V.C.X.; Luo, W.C.; Ye Q.; Thoolen, M. "Column-Switching in High-Performance Liquid Chromatography with Tandem Mass Spectrometric Detection for High-Throughput Preclinical Pharmacokinetic Studies," J. Chromatogr. A. 828, 141-148 (1998).
64. Zell, M.; Husser, C.; Hopfgartner, G. "Column-Switching High-Performance Liquid Chromatography Combined with Ionspray Tandem Mass Spectrometry for the Simultaneous Determination of the Platelet Inhibitor Ro 44-3888 and Its Pro-Drug and Precursor Metabolite in Plasma," J. Mass Spectrom. 32, 23-32 (1997).
65. Boos, K.-S.; Rudolphi, A. "The Use of Restricted-Access Media in HPLC, Part I-Classification and Review," LC-GC 15, 602-611 (1997).
66. Hagestam, I.H.; and Pinkerton, T.C. "Internal Surface Reversed-Phase Silica Supports for Liquid Chromatography," Anal. Chem. 57, 1757-1763 (1985).
67. Boppana, V.K.; Miller-Stein, C.; Schaefer, W.H. "Direct Plasma Liquid Chromatographic-Tandem Mass Spectrometric Analysis of Ganisetron and its 7-Hydroxy Metabolite Utilizing Internal Surface Reversed-Phase Guard Columns and Automated Column-switching Devices," J. Chromatogr. B. 678, 227-236 (1996).
68. Boos, K.-S.;Walfort, A.; Eisenbeiss, F.; Lubda, D. German Patent DE 4130475 (1991).
69. Boos, K.-S.; Rudolphi, A.; Vielhauer, S.;Walfort, A.; Lubda, D.; Eisenbeiss, F. "Alkyl-Diol Silica (ADS): Restricted Access Precolumn Packings for Direct Injection and Coupled-Column Chromatography of Biofluids," Fresenius J. Anal. Chem. 352, 684-690 (1995).
70. Hsieh, Y.; Bryant, M.S.; Gruela, G.; Brisson, J.-M; Korfmacher, W.A. "Direct Analysis of Plasma Samples for Drug Discovery Compounds Using Mixed-Function Column Liquid Chromatography Tandem Mass Spectrometry," Rapid Commun. Mass Spectrom. 14, 1384-1390 (2000).
71. Quin, H.M.; Takarewski, J.J. Int. Patent Number WO 97/16724 (1997).
72. Ayrton, J.; Dear, G.J.; Leavens, W.J.; Mallett, D.N.; Plumb, R.S. "The Use of Turbulent Flow Chromatography/Mass Spectrometry for the Rapid, Direct Analysis of a Novel Pharmaceutical Compound in Plasma," Rapid Commun. Mass Spectrom. 11, 1953-1958 (1997).
73. Jemal, M.; Qing, Y.; Whigan, D.B. "The Use of High-Flow High Performance Liquid Chromatography Coupled with Positive and Negative Ion Electrospray Tandem Mass Spectrometry for Quantitative Bioanalysis via Direct Injection of the Plasma/Serum Samples," Rapid Commun. Mass Spectrom. 12, 1389-1399 (1998).
74. Jemal, M.; Huang, M.; Jiang, X.; Mao, Y.; Powell, M.L. "Direct InjectionVersus Liquid-Liquid Extraction for Plasma Sample Analysis by High Performance Liquid Chromatography with Tandem Mass Spectrometry," Rapid Commun. Mass Spectrom. 13, 2125-2132 (1999).
75. Wu, J.-T.; Zeng, H.; Qian, M.; Brogdon, B.; Unger, S.E. "Direct Plasma Sample Injection in Multiple-Component LC-MS-MS Assays for High-Throughput Pharmacokinetic Screening," Anal. Chem. 72, 61-67 (2000).
76. Ayrton, J.; Clare, R.A.; Dear, G.J.; Mallett, D.N.; Plumb, R.S. "Ultra-High Flow Rate Capillary Liquid Chromatography with Mass Spectrometric Detection for the Direct Analysis of Pharmaceuticals in Plasma at Sub-Nanogram per Milliliter Concentrations," Rapid Commun. Mass Spectrom. 13, 1657-1662 (1999).
77. Bayliss, M.K.; Little, D.; Mallett, D.N.; Plumb, R.S. "Parallel Ultra-High Flow Rate Liquid Chromatography with Mass Spectrometric Detection Using a Multiplex Electrospray Source for Direct, Sensitive Determination of Pharmaceuticals in Plasma at Extremely High Throughput," Rapid Commun. Mass Spectrom. 14, 2039-2045 (2000).
78. King, R.C.; Miller-Stein, C.; Magiera, D.J.; Brann, J. "Description and Validation of a Staggered Parallel High Performance Liquid Chromatography System for Good Laboratory Practice Level Quantitative Analysis by Liquid Chromatography/Tandem Mass Spectrometry," Rapid Commun. Mass Spectrom. 16, 43-52 (2002).
79. Grant, R.P.; Cameron, C.; Mackenzie-McMurter, S. "Generic Serial and Parallel On-Line Direct-Injection Using Turbulent Flow Liquid Chromatography/Tandem Mass Spectrometry," Rapid Commun. Mass Spectrom. 16, 1785-1792 (2002).
80. Zhang, H.; Heinig, K.; Henion, J. "Atmospheric Pressure Ionization Time-of-Flight Mass Spectrometry Coupled with Fast Liquid Chromatography for Quantitation and Accurate Mass Measurement of Five Pharmaceutical Drugs," J. Mass Spectrom. 35, 423-431 (2000).
81. Warner, D.L.; Dorsey, J.G. "Reduction of Total Analysis Time in Gradient Elution, Reversed-Phase Liquid Chromatography," LC-GC 15, 254-262 (1997).
82. Hopfgartner, G.; Bean, K.; Henion, J.; Henry, R. "Ion Spray Mass Spectrometric Detection for Liquid Chromatography: A Concentration-or a Mass-Flow-Sensitive Device?" J. Chromatogr. 647, 51-61 (1993).
83. Plumb, R.S.; Dear, G.J.; Mallett, D.; Fraser, I.J.;Ayrton, J.; Ioannou, C. "The Application of Fast Gradient Capillary Liquid Chromatography/Mass Spectrometry to the Analysis of Pharmaceuticals in Biofluids," Rapid Commun. Mass Spectrom. 13, 865-872 (1999).
84. Romanyshyn, L.; Tiller, P.R.; Hop, E.C.A. "Bioanalytical Applications of 'Fast Chromatography' to High-Throughput Liquid Chromatography/Tandem Mass Spectrometric Quantitation," Rapid Commun. Mass Spectrom. 14, 1662-1668 (2000).
85. Romanyshyn, L.; Tiller, P.R.; Alvaro, R.; Pereira, A.; Hop, C.E.C.A "Ultra-Fast Gradient vs. Fast Isocratic Chromatography in Bioanalytical Quantification by Liquid Chromatography/Tandem Mass Spectrometry," Rapid Commun. Mass Spectrom. 15, 313-319 (2001).
86. Cheng, Y.-F.; Lu, Z.; Neue, U. "Ultrafast Liquid Chromatography/Ultraviolet and Liquid Chromatography/Tandem Mass Spectrometric Analysis," Rapid Commun. Mass Spectrom. 15, 141-151 (2001).
87. Hayward, M.J.; Munson, J.L.; Conneely, G.; Hargiss, L.O. "What Limits Productivity in High Flow Fast LC/MS? " in Proceedings of the 49th ASMS Conference on Mass Spectrometry and Allied Topics, Chicago, IL, May 27-31, 2001.
88. Murphy, A.T.; Berna, M.J.; Holsapple, J.L.; Ackermann, B.L. "Effects of Flow Rate on High-Throughput Quantitative Analysis of Protein-Precipitated Plasma Using Liquid Chromatography/Tandem Mass Spectrometry," Rapid Commun. Mass Spectrom. 16, 537-543 (2002).
89. Covey, T.; Stott, B.; Joliffe, C.; Thomson, B. "Development of a High Sensitivity Triple Quadrupole Instrument for Quantitative Analysis," in Proceedings of the 46th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, FL, May 31-June 5, 1998.
90. Minakuchi, H.; Nakanishi, K.; Soga, N.; Ishizuka, N.; Tanaka, N. "Octadecylsilylated Porous Silica Rods as Separation Media for Reversed-Phase Liquid Chromatography," Anal. Chem. 68, 3498-3501 (1996).
91. Tanaka, N.; Nagayama, H.; Kobayashi, H.; Ikegami, T.; Hosoya, K.; Ishizuka, N.; Minakuchi, H.; Nakanishi, K.; Cabrera, K.; Lubda, D. "Monolithic Silica Columns for HPLC, micro-HPLC and CEC," J. High Resol. Chromatogr. 23, 111-116 (2000).
92. Wu, J.-T.; Zeng, H.; Deng, Y.; Unger, S.E. "High-Speed Liquid Chromatography/Tandem Mass Spectrometry Using a Monolithic Column for High-Throughput Bioanalysis," Rapid Commun. Mass Spectrom. 15, 1113-1119 (2001).
93. Barbarin, N.; Mawhinney, D.B.; Black, R.; Henion, J.; "High-Throughput Selected Reaction Monitoring Liquid Chromatography-Mass Spectrometry Determination Of Methylphenidate and its Major Metabolite, Ritalinic Acid, in Rat Plasma Employing Monolithic Columns," J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 783, 73-83 (2003).
94. Przybyciel, M.; Majors, R.E. "Phase Collapse in Reversed-Phase Liquid Chromatography," LC-GC 20, 516-523 (2002).
95. Majors, R.E.; Przybyciel, M. "Columns for Reversed-Phase LC Separations in Highly Aqueous Mobile Phases," LC-GC 20, 584-593 (2002).
96. Miller-Stein, C.; Fernandez-Metzler, C. "Determination of Chiral Sulfoxides in Plasma by Normal-Phase Liquid Chromatography-Atmospheric Pressure Chemical Ionization Mass Spectrometry," J. Chromatogr. A 964, 161-168 (2002).
97. Strege, M.A.; Stevenson, S.; Lawrence, S.M. "Mixed-Mode Anion-Cation Exchange/Hydrophilic Interaction Liquid Chromatography-Electrospray Mass Spectrometry as an Alternative to Reversed Phase for Small Molecule Drug Discovery," Anal. Chem. 72, 4629-4633 (2000).
98. Naidong, W.; Lee, J.W.; Jiang, X.; Wehling, M.; Hulse, J.D.; Lin, P.P. "Simultaneous Assay of Morphine, Morphine-3-Glucuronide and Morphine-6-Glucuronide in Human Plasma Using Normal-Phase Liquid Chromatography-Tandem Mass Spectrometry with a Silica Column and an Aqueous Organic Mobile Phase," J. Chromatogr. B Biomed. Sci Appl. 735, 255-269 (1999).
99. Shou, W.Z.; Chen, Y.L.; Eerkes, A.; Tang, Y.Q.; Magis, L.; Jiang, X.; Naidong, W. "Ultrafast Liquid Chromatography/Tandem Mass Spectrometry Bioanalysis of Polar Analytes Using Packed Silica Columns," Rapid Commun. Mass Spectrom. 16, 1613-1621 (2002).
100. Korfmacher, W.A.; Veals, J.; Dunn-Meynell, K.; Zhang, X.P.; Tucker, G.; Cox, K.A.; Lin, C.C. "Demonstration of the Capabilities of a Parallel High Performance Liquid Chromatography Tandem Mass Spectrometry System for Use in the Analysis of Drug Discovery Samples," Rapid Commun. Mass Spectrom. 13, 1991-1999 (1999).
101. Van Pelt, C.K.; Corso, T.N.; Schultz, G.A.; Lowes, S.; Henion, J. "A Four-Column Parallel Chromatography System for Isocratic or Gradient LC/MS Analyses," Anal. Chem. 73, 582-588 (2001).
102. Yang, L.; Mann, T.D.; Little, D.; Wu, N.; Clement, R.P.; Rudewicz, P.J. "Evaluation of a Four-Channel Multiplexed Electrospray Triple Quadrupole Mass Spectrometer for the Simultaneous Validation of LC/MS/MS Methods in Four Different Preclinical Matrices," Anal. Chem. 73, 1740-1747 (2001).
103. Deng, T.; Zeng, H.; Unger, S.E.;Wu, J.T. "Multiple-Sprayer Tandem Mass Spectrometry with Parallel High Flow Extraction and Parallel Separation for High-Throughput Quantitation in Biological Fluids," Rapid Commun. Mass Spectrom. 15, 1634-1640 (2001).
104. Zeng, H.; Wu, J.T.; Unger, S.E. "The Investigation and the Use of High Flow Column-Switching LC/MS/MS as a High-Throughput Approach for Direct Plasma Sample Analysis of Single and Multiple Components in Pharmacokinetic Studies," J. Pharm. Biomed. Anal. 27, 967-982 (2002).
105. Deng, Y.; Wu, J.T.; Lloyd, T.L.; Chi, C.L.; Olah, T.V.; Unger, S.E. "High-Speed Gradient Parallel Liquid Chromatography/Tandem Mass Spectrometry with Fully Automated Sample Preparation for Bioanalysis: 30 Seconds per Sample from Plasma," Rapid Commun. Mass Spectrom. 16, 1116-1123 (2002).
106. Whalen, K.M.; Rogers, K.J.; Cole, M.J.; Janiszewski, J.S. "AutoScan: An AutomatedWorkstation for Rapid Determination of Mass and Tandem Mass Spectrometry Conditions for Quantitative Bioanalytical Mass Spectrometry," Rapid Commun. Mass Spectrom. 14, 2074-2079 (2000).
107. Chen, S.; Carvey, R. "Validation of Liquid-Liquid Extraction Followed by Flow-Injection Negative Ion Electrospray Mass Spectrometry Assay to Topiramate in Human Plasma," Rapid Commun. Mass Spectrom. 15, 159-163 (2001).
108. Zheng, J.J.; Lynch, E.D.; Unger, S.E. "Comparison of SPE and Fast LC to Eliminate Mass Spectrometric Matrix Effects from Microsomal Incubation Products," J. Pharm. Biomed. Anal. 28, 279-285 (2002).
109. Olech, R.M.; Pranis, R.A.; Jacobson, J.R.; Perman, C.A.; Boman, B.A.; Soldo, J.; Speziale, R.; Astle, T.W.; Cole, M.J.; Janiszewski, J.S.; Whalen, K.M. "A Novel SPE System for High-Throughput Quantification by ESI-LC/MS/MS Utilizing 96 Discrete Zones in a Disposable Card Format," in Proceedings of the 49th Conference on Mass Spectrometry and Allied Topics, Chicago, IL, May 27-31, 2001.
110. Dethy, J.M.; Ackermann, B.L.; Delatour, C.; Henion, J.D.; Schultz, G.A. "Demonstration of Direct Bioanalysis of Drugs in Plasma Using Nanoelectrospray Infusion From a Silicon Chip Coupled with Tandem Mass Spectrometry," Anal. Chem. 75, 805-811 (2003).
111. Berman, J.; Halm, K.; Adkison, K.; Shaffer, J. "Simultaneous Pharmacokinetic Screening of a Mixture of Compounds in the Dog Using API LC/MS/MS Analysis for Increased Throughput," J. Med. Chem. 40, 3-5 (1997).
112. Olah, T.V.; McLoughlin, D.A.; Gilbert, J.D. "The Simultaneous Determination of Mixtures of Drug Candidates by Liquid Chromatography/Atmospheric Pressure Chemical Ionization Mass Spectrometry as an In Vivo Drug Screening Procedure," Rapid Commun. Mass Spectrom. 11, 17-23 (1997).
113. Tong, X.; Ita, I.E.; Wang, J.; Pivnichny, J.V. "Characterization of a Technique for Rapid Pharmacokinetic Studies of Multiple Co-Eluting Compounds by LC/MS/MS," J. Pharm. Biomed. Anal. 29, 773-784 (1999).
114. White, R.E.; Manitpisitkul, P. "Pharmacokinetic Theory of Cassette Dosing in Drug Discovery Screening," Drug Metab. Dispos. 29, 957-966 (2001).
115. Hop, C.E.C.A; Wang, Z.; Chen, Q.; Kwei, G. "Plasma-Pooling Methods to Increase Throughput for In Vivo Pharmacokinetic Screening," J. Pharm. Sci. 87, 901-903 (1998).
116. Zhang, N.; Rogers, K.; Gajda, K.; Kagel, J.R.; Rossi, D.T. "Integrated Sample Collection and Handling for Drug Discovery Bioanalysis," J. Pharm. Biomed. Anal. 23, 551-560 (2000).
117. Sadagopan, N.P.; Li, W.; Cook, J.A.; Galvan, B.; Weller, D.L.; Fountain, S.T.; Cohen, L.H. "Investigation of EDTA Anticoagulant in Plasma to Improve the Throughput of Liquid Chromatography/Tandem Mass Spectrometric Assays," Rapid Commun. Mass Spectrom. 17, 1065-1070 (2003).
118. Berna, M.J.; Murphy, A.T.;Wilken, B.F.; Ackermann, B.L. "Collection, Storage and Filtration of In-Vivo Study Samples Using 96-Well Filter Plates to Facilitate Automated Sample Preparation and LC/MS/MS Analysis," Anal. Chem. 74, 1197-1201 (2002).
119. Korfmacher, W.A.; Cox, K.A.; Ng, K.J.; Veals, J.; Hsieh, Y.; Wainhaus, S.; Broske, L.; Prelusky, D.; Nomeir, A.; White, R.E. "Cassette-Accelerated Rapid Rat Screen: A Systematic Procedure for the Dosing and Liquid Chromatography/Atmospheric Pressure Ionization Tandem Mass Spectrometric Analysis of New Chemical Entities as Part of New Drug Discovery," Rapid Commun. Mass Spectrom. 15, 335-340 (2001).
120. Buhrman, D.L.; Price, P.I.; Rudewicz, P.J. "Quantitation of SR 27417 in Human Plasma Using Electrospray Liquid Chromatography-Tandem Mass Spectrometry: A Study of Ion Suppression," J. Am. Soc. Mass Spectrom. 7, 1099-1105 (1996).
121. LeBlanc, J.C.Y.; Liu, C.C.; Covey, T.; Kovarik, P.; Thompson, C.; Javahari, H.; Jong, R. "Ion Suppression: Parameters That Influence the Ionization Efficiency in APCI-LC/MS/MS," in Proceedings of the 49th ASMS Conference on Mass Spectrometry and Allied Topics, Chicago, IL, May 27-31, 2001.
122. Shang, J.X.; Zhong, W.-Z.; Heath, T.G. "Examination of Matrix-Induced Ionization Suppression in Atmospheric Pressure Chemical Ionization," in Proceedings of the 49th ASMS Conference on Mass Spectrometry and Allied Topics, Chicago, IL, May 27-31, 2001.
123. Bonfiglio, R.; King, R.C.; Olah, T.V.; Merkle, K. "The Effect of Sample Preparation Methods on the Variability of the Electrospray Ionization Response for Model Drug Compounds," Rapid Commun. Mass Spectrom. 13, 1175-1185 (1999).
124. Mei, H.; Hsieh, Y.; Nardo, C.; Xu, X.;Wang, S.; Ng, K.; Korfmacher, W.A. "Investigation of Matrix Effects in Bioanalytical High-Performance Liquid Chromatography/Tandem Mass Spectrometric Assays: Application to Drug Discovery," Rapid Commun. Mass Spectrom. 17, 97-103 (2003).
125. Tong, X.S.; Wang, J.; Zheng, S.; Pivnichny, J.V.; Griffin, P.R.; Shen, X.; Donnelly, M.; Vakerich, K.; Nunes, C.; Fenyk-Melody, J. "Effect of Signal Interference from Dosing Excipients on Pharmacokinetic Screening of Drug Candidates by Liquid Chromatography/Mass Spectrometry," Anal. Chem. 74, 6305-6313 (2002).
126. Shou, W.Z.; Naidong, W. "Post-Column Infusion Study of the 'Dosing Vehicle Effect' in the Liquid Chromatography/Tandem Mass Spectrometric Analysis of Discovery Pharmacokinetic Samples," Rapid Commun. Mass Spectrom. 17, 589-597 (2003).
127. Avery, M.J. "Quantitative Characterization of Differential Ion Suppression on Liquid Chromatography/Atmospheric Pressure Ionization Mass Spectrometric Bioanalytical Methods," Rapid Commun. Mass Spectrom. 17, 197-201 (2003).
128. Ramanathan, R.; Su, A.D.; Alvarez, N.; Blumenkrantz, N.; Chowdhury, S.K.; Alton, K.; Patrick, J. "Liquid Chromatography/Mass Spectrometry Methods for Distinguishing N-Oxides from Hydroxylated Compounds," Anal. Chem. 72, 1352-1359 (2000).
129. Tong, W.; Chowdhury, S.K.; Chen, J.C.; Zhong, R.; Alton, K.B.; Patrick, J.E. "Fragmentation of N-Oxides (Deoxygenation) in Atmospheric Pressure Ionization: Investigation of the Activation Process," Rapid. Commun. Mass Spectrom. 15, 2085-2090 (2001).
130. Jemal, M.; Quyang, Z. "The Need for Chromatographic and Mass Resolution in Liquid Chromatography/Tandem Mass Spectrometric Methods Used for Quantitation of Lactones and Corresponding Hydroxy Acids in Biological Samples," Rapid Commun. Mass Spectrom. 14, 1757-1765 (2000).
131. Gobey, J.S.; Avery, M.J. "The Impact of Metabolites on LC/MS/MS Assays: A Real Life Example," in Proceedings of the 49th ASMS Conference on Mass Spectrometry and Allied Topics, Chicago, IL, May 27-31, 2001.
132. Jemal, M.; Ouyang, Z.; Powell, M.L. "A Strategy for a Post-Method-Validation use of Incurred Biological Samples for Establishing the Acceptability of a Liquid Chromatography/Tandem Mass-Spectrometric Method for Quantitation of Drugs in Biological Samples," Rapid Commun. Mass Spectrom. 16, 1538-1547 (2002).
133. Schultz, G.A.; Corso, T.N.; Prosser, S.J.; Zhang, S. "A Fully Integrated Monolithic Microchip Electrospray Device for Mass Spectrometry," Anal. Chem. 72, 4058-4063 (2000).