Mass spectrometry innovations in drug discovery and development

Pharmaceutical Research

Volumn 18, Issue 2, 2001, Pages 131-145

  Papac, Damon I ^a   Shahrokh, Zahra ^b  

^a NPS Pharmaceutical Inc   (United States)

^b GENENTECH INC   (United States)

Author keywords

Biomolecule characterization; Drug development; High throughput screening; Mass balance; Mass spectrometry; Metabolite identification; Pharmacokinetics

Indexed keywords

DRUG;

ACCURACY; BIOTECHNOLOGY; COMPUTER SYSTEM; DRUG DETERMINATION; DRUG INDUSTRY; DRUG SCREENING; MASS SPECTROMETRY; PRIORITY JOURNAL; REVIEW;

DRUG DESIGN; HUMANS; MASS SPECTROMETRY; MOLECULAR WEIGHT; PHARMACOKINETICS;

EID: 0034954468     PISSN: 07248741     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1011049231231     Document Type: Review

References (116)

1. Strategies and recent technologies in drug discovery
2. Electrospray interface for liquid chromatographs and mass spectrometers
3. Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons
4. Ion-spray mass spectrometry of marine toxins. III. Analysis of paralytic shellfish poisoning toxins by flow-injection analysis, liquid chromatography/mass spectrometry and capillary electrophoresis/mass spectrometry
5. A new UltraFast FIA-MS method for microtiter plate analysis using an eight probe injection system
6. Developments of a fully automated parallel HPLC/mass spectrometry system for the analytical characterization and preparative purification of combinatorial libraries
7. High throughput liquid chromatography/mass spectrometric analyses using a novel multiplexed electrospray interface
8. UltraFast HPLC/MS for the identification and characterization of combinatorial library compounds
9. Automated exact mass measurements of combinatorial libraries by ESI-TOF-MS
10. Packed column supercritical fluid chromatography/mass spectrometry for high-throughput analysis. Part 2
11. High-speed screening of combinatorial libraries by gradient packed-column supercritical fluid chromatography
12. Application of evaporative light scattering detection to the characterization of combinatorial and parallel synthesis libraries for pharmaceutical drug discovery
13. The evaporative light scattering detector: A universal instrument for non volatile solutes in LC and SFC
14. High-throughput characterization of combinatorial libraries
15. Optimizing quality control of combinatorial libraries with SFC/MS
16. High throughput purification of combinatorial libraries
17. Identifying small-molecule lead compounds: The screening approach to drug discovery
18. Affinity capillary electrophoresis-mass spectrometry for screening combinatorial libraries
19. Micellar electrokinetic chromatography-mass spectrometry
20. Screening for high-affinity ligands to the SRC SH2 domain using capillary isoelectric focusing-electrospray ionization ion trap mass spectrometry
21. Screening solution-phase combinatorial libraries using pulsed ultrafiltration/electrospray mass spectrometry
22. Characterization of SH2-ligand interactions via library affinity selection with mass spectrometric detection
23. Characterization of benzodiazepine "combinatorial" chemical libraries by on-line immunoaffinity extraction, coupled column HPLC-ion spray mass spectrometry-tandem mass spectrometry
24. Affinity selection and mass spectrometry-based strategies to identify lead compounds in combinatorial libraries
25. An overview of developability considerations in lead selection and optimization
26. Atmospheric pressure ionization LC/MS/MS techniques for drug disposition studies
27. 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
28. High throughput liquid chromatography/mass spectrometry bioanalysis using 96-well disk solid phase extraction plate for the sample preparation
29. Column-switching high-performance liquid chromatography combined with ion-spray tandem mass spectrometry for the simultaneous determination of the platelet inhibitor Ro 44-3888 and its pro-drug and precursor metabolite in plasma
30. Determination of Pranlukast and its metabolites in human plasma by LC/MS/MS with PROSPEKT on-line solid-phase extraction
31. Column switching in high-performance liquid chromatography with tandem mass spectrometric detection for high-throughput preclinical pharmacokinetic studies
32. Liquid chromatography-mass spectrometry with on-line solid-phase extraction by a restricted-access C18 precolumn for direct plasma and urine injection
33. Use of Caco-2 cells and LC/MS/MS to screen a peptide combinatorial library for permeable structures
34. Development of an automated mass spectrometry system for the quantitative analysis of liver microsomal incubation samples: A tool for rapid screening of new compounds for metabolic stability
35. Assays of ligand-human serum albumin binding using pulsed ultrafiltration and liquid chromatography-mass spectrometry
36. Accelerated stability screens for drug optimization
37. Cassette dosing: Rapid in vivo assessment of pharmacokinetics
38. Application of LC-MS/MS quantitative analytical methods to drug metabolism studies in drug discovery
39. Plasma-pooling methods to increase throughput for in vivo pharmacokinetic screening
40. Sample pooling to expedite bioanalysis and pharmacokinetic research
41. The use of stable isotope labeling and liquid chromatography-tandem mass spectrometry techniques to simultaneously determine the oral and ophthalmic bioavailability of timolol in dogs
42. Moricizine bioavailability via simultaneous, dual, stable isotope administration: Bioequivalence implications
43. Quantification and rapid metabolite identification in drug discovery using API time-of-flight LC/MS
44. Metabolite profiling study of propranolol in rat using LC/MS/MS analysis
45. Structure elucidation of three isomeric metabolites of SYN-2836, a novel antifungal agent, in dogs via liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry methodologies
46. Identification of in vitro metabolites of Indinavir by "intelligent automated LC-MS/MS" (INTAMS) utilizing triple quadrupole tandem mass spectrometry
47. Rapid liquid chromatography with tandem mass spectrometry-based screening procedures for studies on the biotransformation of drug candidates
48. Application of liquid chromatography-mass spectrometry(n) analyses to the characterization of novel glyburide metabolites formed in vitro
49. The rapid identification of drug metabolites using capillary liquid chromatography coupled to an ion trap mass spectrometer
50. Exact mass measurement of product ions for the structural elucidation of drug metabolites with a tandem quadrupole orthogonal-acceleration time-of-flight mass spectrometer
51. Rapid drug metabolite profiling using fast liquid chromatography, automated multiple-stage mass spectrometry and receptor-binding
52. Accelerator mass spectrometry
53. Analytical performance of accelerator mass spectrometry and liquid scintillation counting for detection of 14C-labeled atrazine metabolites in human urine
54. Biomedical applications of accelerator mass spectrometry isotope measurements at the level of the atom
55. Evaluation of isotope ratio (IR) mass spectrometry for the study of drug metabolism
56. Performance of human mass balance studies with stable isotope-labeled drug and continuous flow-isotope ratio mass spectrometry: A progress report
57. High-precision continuous-flow isotope ratio mass spectrometry
58. CRIMS: Chemical reaction interface mass spectrometry
59. Replacing 14C with stable isotopes in drug metabolism studies
60. Liquid chromatography/chemical reaction interface mass spectrometry as an alternative to radioisotopes for quantitative drug metabolism studies
61. Flow injection with chemical reaction interface-isotope ratio mass spectrometry: An alternative to off-line combustion for detecting low levels of enriched 13C in mass balance studies
62. Pharmacokinetic and metabolism studies using uniformly stable isotope labeled proteins with HPLC/CRIMS detection
63. Mass spectrometry and the age of the proteome
64. An integrated approach to proteome analysis: Identification of proteins associated with cardiac hypertrophy
65. Strategies in proteome research
66. Proteome analysis of glycoforms: A review of strategies for the microcharacterisation of glycoproteins separated by two-dimensional polyacrylamide gel electrophoresis
67. Identifying proteins and posttranslational modifications by mass spectrometry
68. Protein identification by peptide mass fingerprinting
69. Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases
70. Use of mass spectrometric molecular weight information to identify proteins in sequence databases
71. Peptide mass maps: A highly informative approach to protein identification
72. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database
73. Error-tolerant identification of peptides in sequence databases by peptide sequence tags
74. The quadrupole ion trap mass spectrometer - A small solution to a big challenge
75. Post-source decay analysis in matrix-assisted laser desorption/ionization mass spectrometry of biomolecules
76. Analytical properties of the nanoelectrospray ion source
77. Accurate mass measurements using MALDI-TOF with delayed extraction
78. Role of accurate mass measurement (+/- 10 ppm) in protein identification strategies employing MS or MS/MS and database searching
79. Reliable automatic protein identification from matrix-assisted laser desorption/ionization mass spectrometric peptide fingerprints
80. Towards an automated approach for protein identification in proteome projects
81. Coupling capillary HPLC to MALDI and N-terminal sequencing of peptides via automated microblotting onto membrane substrates
82. Off-line coupling of capillary electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
83. A rotating ball inlet for on-line MALDI mass spectrometry
84. A novel interface for on-line coupling of liquid capillary chromatography with matrix-assisted laser desorption/ionization detection
85. Capillary electrophoresis/electrospray ionization high mass accuracy time-of-flight mass spectrometry for protein identification using peptide mapping
86. Electrophoresis combined with novel mass spectrometry techniques: Powerful tools for the analysis of proteins and proteomes
87. A novel geometry mass spectrometry, the Q-TOF, for low-femtomole/attomole-range biopolmer sequencing
88. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags
89. Applications of new analytical technology to the production of a "well characterized biological"
90. Application of capillary electrophoresis, liquid chromatography, electrospray-mass spectrometry and matrix-assisted laser desorption/ionization - Time of flight - Mass spectrometry to the characterization of recombinant human erythropoietin
91. The use of sequential high-performance liquid chromatography and capillary zone electrophoresis to separate the glycosylated peptides from recombinant tissue plasminogen activator to a detailed level of microheterogeneity
92. Characterization of the tryptic map of recombinant DNA derived tissue plasminogen activator by high-performance liquid chromatography-electrospray ionization mass spectrometry
93. High-sensitivity analysis and sequencing of peptides and proteins by quadrupole ion trap mass spectrometry
94. Differentiation of "isobaric" peptides and human milk oligosaccharides by exact mass measurements using electrospray ionization orthogonal time-of-flight analysis
95. Mapping of recombinant hemoglobin using immobilized trypsin cartridges
96. Cell line and site specific comparative analysis of the N-linked oligosaccharides on human ICAM-1des454-532 by electrospray ionization mass spectrometry
97. The glycosylation heterogeneity of recombinant human IFN-γ
98. Characterization of tyrosine sulfate residues in antihemophilic recombinant factor VIII by liquid chromatography electrospray ionization tandem mass spectrometry and amino acid analysis
99. Development of disulfide peptide mapping and determination of disulfide structure of recombinant human osteoprotegerin chimera produced in Escherichia coli
100. Formulation development and primary degradation pathways for recombinant human nerve growth factor
101. Consideration of conformational transition and racemization during process development of recombinant glucagon-like peptide-1
102. Susceptibility of rhDNase I to glycation in the dry-powder state
103. Matrix-assisted laser desorption mass spectrometric analysis of a pegylated recombinant protein
104. Strategies for locating disulfide bonds in a monoclonal antibody via mass spectrometry
105. Disulfide structure of the heparin binding domain in vascular endothelial growth factor: Characterization of posttranslational modifications in VEGF
106. Optimization of the cleavage reaction for cyanylated cysteinyl proteins for efficient and simplified mass mapping
107. The use of high-performance anion-exchange chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to monitor and identify oligosaccharide degradation
108. Simplified identification of monoclonal antibodies and glycoproteins by mass spectrometry for production control systems
109. Analysis of hybridoma cell culture processes by SDS/gel capillary electrophoresis and matrix-assisted laser desorption ionization-time-of-flight MS
110. Peptide mapping by MALDI-TOF-MS of recombinant protein pharmaceuticals as QC lot release test
111. Biotechnology Pharmaceuticals 2000
112. Monitoring glycosylation levels of a recombinant antibody using electrospray mass spectrometry with selective ion-monitoring
113. Ciphergen's PBS-1 boosts Alzheimer's research
114. Revolution of the drug discovery process using laboratory-on-a-chip technology