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IAM References

  1. Pidgeon, C. and Venkataram, U.V. (1989) Immobilized artificial membrane chromatography: supports composed of membrane lipids. Anal. Biochem. 176, 36-47.
  2. Markovich, R.J., Stevens, J.M. and Pidgeon, C. (1989) Fourier transform infrared assay of membrane lipids immobilized to silica: leaching and stability of immobilized artificial membrane-bonded phases. Anal. Biochem. 182, 237-44.
  3. Stevens, J.M., Markovich, R.J. and Pidgeon, C. (1989) Characterization of immobilized artificial membrane HPLC columns using deoxy nucleotides as model compounds. BioChromatography 4, 192-205.
  4. Pidgeon, C. (1990) Immobilized artificial membrane. U.S. Patent 4,931,498.
  5. Pidgeon, C. (1990) Solid phase membrane mimetics: immobilized artificial membranes. Enzyme Microb Technol 12, 149-50.
  6. Pidgeon, C. (1990) Method for solid membrane mimetics. U.S. Patent 4,927,879.
  7. Markovich, R.J., Qui, X.X., Nichols, D.E., Pidgeon, C., Invergo, B. and Alvarez, F.M. (1991) Silica subsurface amine effect on the chemical stability and chromatographic properties of end-capped immobilized artificial membrane surfaces. Anal. Chem. 63, 1851-60.
  8. Pidgeon, C., Stevens, J., Otto, S., Jefcoate, C. and Marcus, C. (1991) Immobilized artificial membrane chromatography: rapid purification of functional membrane proteins. Anal. Biochem. 194, 163-73.
  9. Pidgeon, C., Marcus, C. and Alvarez, F. (1991) Immobilized artificial membrane chromatography: surface chemistry and applications. presented at Appl. Enzyme Biotechnol., [Proc. Tex. A&M Univ., IUCCP Symp.], 9th, pp. 201-20.
  10. Chae, W.G., Luo, C., Rhee, D.M., Lombardo, C.R., Low, P. and Pidgeon, C. (1991) Immobilized artificial membrane chromatography. Initial studies using monomyristoylphosphatidylcholine as a detergent for solubilizing and purifying membrane proteins. Recent Adv. Phytochem. 25, 149-74.
  11. Otto, S., Bhattacharyya. K.K. and Jefcoate, C. R. (1992) Polycyclic aromatic hydrocarbon metabolism in rat adrenal, ovary, and testis microsomes is catalyzed by the same novel cytochrome P450 (P450RAP). Endocrinology131, 3067-76.
  12. Chui, W.K. and Wainer, I.W. (1992) Enzyme-based high-performance liquid chromatography supports as probes of enzyme activity and inhibition: the immobilization of trypsin and alpha-chymotrypsin on an immobilized artificial membrane high-performance liquid chromatography support. Anal. Biochem. 201, 237-45.
  13. Qui, X. and Pidgeon, C. (1993) A phosphorus-31 NMR study of immobilized artificial membrane surfaces: structure and dynamics of immobilized phospholipids.  J. Phys. Chem. 97, 12399-407.
  14. Alebic-Kolbah, T. and Wainer, I.W. (1993) Microsomal immobilized-enzyme-reactor for online production of glucuronides in a HPLC column. Chromatographia 37, 608-12.
  15. Kaliszan, R., Kaliszan, A. and Wainer, I.W. (1993) Deactivated hydrocarbonaceous silica and immobilized artificial membrane stationary phases in high-performance liquid chromatographic determination of hydrophobicities of organic bases: relationship to Log P and CLOGP. J. Pharm. Biomed. Anal. 11, 505-11.
  16. Alebic-Kolbah, T. and Wainer, I.W. (1993) Enzyme-based high-performance liquid chromatography stationary phases as metabolic reactors. Immobilization of nonsolubilized rat liver microsomes on an immobilized artificial membrane high-performance liquid chromatography support. J. Chromatogr. 646, 289-95.
  17. Alvarez, F.M., Bottom, C.B., Chikhale, P. and Pidgeon, C. (1993) Immobilized artificial membrane chromatography: prediction of drug transport across biological barriers. Mol. Interact. Biosep. 151-67.
  18. Alebic-Kolbah, T. and Wainer, I.W. (1993) Application of an enzyme-based stationary phase to the determination of enzyme kinetic constants and types of inhibition. New high-performance liquid chromatographic approach utilizing an immobilized artificial membrane chromatographic support. J. Chromatogr.653, 122-9.
  19. Kaliszan, R. (1994) Chemometric analysis of biochromatographic data: implications for molecular pharmacology. Chemom. Intell. Lab. Syst. 24, 89-97.
  20. Kaliszan, R., Nasal, A. and Bucinski, A. (1994) Chromatographic hydrophobicity parameter determined on an immobilized artificial membrane column: relationships to standard measures of hydrophobicity and bioactivity. Eur. J. Med. Chem. 29, 163-70.
  21. Pidgeon, C., Ong, S., Choi, H. and Liu, H. (1994) Preparation of mixed ligand immobilized artificial membranes for predicting drug binding to membranes. Anal. Chem. 66, 2701-9.
  22. Ong, S., Cai, S.J., Bernal, C., Rhee, D., Qui, X. and Pidgeon, C. (1994) Phospholipid Immobilization on Solid Surfaces. Anal. Chem. 66, 782-92.
  23. Ong, S., Qui, X. and Pidgeon, C. (1994) Solute Interactions with Immobilized Artificial Membranes. J. Phys.Chem. 98, 10189-99.
  24. Rhee, D., Markovich, R., Chae, W.G., Qui, X. and Pidgeon, C. (1994) Chromatographic surfaces prepared from lysophosphatidylcholine ligands. Anal. Chim. Acta 297, 377-86.
  25. Nasal, A., Radwanska, A., Osmialowski, K., Bucinski, A., Kaliszan, R., Barker, G.E., Sun, P. and Hartwick, R.A. (1994) Quantitative relationships between the structure of beta-adrenolytic and antihistamine drugs and their retention on an alpha 1-acid glycoprotein HPLC column. Biomed Chromatogr8, 125-9.
  26. Pidgeon, C. and Ong, S. (1995) Predicting drug-membrane interactions. Chemtech25, 38-48.
  27. Radwanska, A., Frackowiak, T., Ibrahim, H., Aubry, A.F. and Kaliszan, R. (1995) Chromatographic modelling of interactions between melanin and phenothiazine and dibenzazepine drugs. Biomed Chromatogr 9, 233-7.
  28. Sheng, Q., Schulten, K. and Pidgeon, C. (1995) Molecular Dynamic Simulation of Immobilized Artificial Membranes. J. Phys. Chem. 99, 11018-27.
  29. Pidgeon. C., Ong, S., Liu, H., Qui, X., Pidgeon, M., Dantzig, A.H., Munroe, J., Hornback, W.J., Kasher, J.S., Glunz, L. and et al. (1995) IAM chromatography: an in vitro screen for predicting drug membrane permeability. J. Med. Chem. 38, 590-4.
  30. Langner, J., Brandt, B., Leibelt, S. and Assman, G. (1995) One-step separation of a hydrophylic and a lipophilic isoform of the tumor-associated DF3-antigen (CA15-3) with immobilized artificial membrane HPLC (IAM.PC HPLC ). J. Exp. Clin. Cancer Res. 14, 293-300.
  31. Ong, S. and Pidgeon, C. (1995) Thermodynamics of solute Partitioning into Immobilized Artificial Membranes. Anal. Chem. 67, 2119-28.
  32. Ong, S., Liu, H., Qui, X., Bhat, G. and Pidgeon, C. (1995) Membrane partition coefficients chromatographically measured using immobilized artificial membrane surfaces. Anal. Chem. 67, 755-62.
  33. Nasal, A., Sznitowska, M., Bucinski, A. and Kaliszan, R. (1995) Hydrophobicity parameter from high-performance liquid chromatography on an immobilized artificial membrane column and its relationship to bioactivity. J. Chromatogr. A 692, 83-9.
  34. Kaliszan, R., Nasal, A., Turowski, M., Radwanska, A. and Bober, L. (1995) Combination of biochromatography and chemometrics: A new research strategy in molecular pharmacology and drug design. presented at Int. Symp. Chromatogr., 35th Anniv. Res. Group Liq. Chromatogr., Japan, pp. 651-62.
  35. Cai, S.J., McAndrew, R.S., Leonard, B.P., Chapman, K.D. and Pidgeon, C. (1995) Rapid purification of cotton seed membrane-bound N-acylphosphatidylethanolamine synthase by immobilized artificial membrane chromatography. J. Chromatogr. A 696, 49-62.
  36. Liu, H.L., Ong, S.W., Glunz, L. and Pidgeon, C. (1995) Predicting Drug Membrane Interactions by HPLC Structural Requirements Of Chromatographic Surfaces. Analytical Chemistry 67, 3550-3557.
  37. Cohen, D.E and Leonard, M.R. (1995) Immobilized artificial membrane chromatography: a rapid and accurate HPLC method for predicting bile salt-membrane interactions. J.Lipid Res. 36, 2251-60.
  38. Kaliszan, R., Nasal, A., Turowski, M., Debont, T., Daenens, P. and Tytgat, J. (1996) Quantitative Structure Retention Relationships In the Examination Of the Topography Of the Binding Site Of Antihistamine Drugs On Alpha(1) Acid Glycoprotein: An Improved Fractionation and Fast Screening Method For the Identification Of New and Selective Neurotoxins. Journal of Chromatography 722, 25-32.
  39. Barbato, F., Larotonda, M.I. and Quaglia, F. (1996) Chromatographic indices determined on an immobilized artificial membrane (IAM) column as descriptors of lipophilic and polar interactions of 4-phenyldihydropyridine calcium-channel blockers with biomembranes. European Journal of Medicinal Chemistry 31, 311-318.
  40. Bernal, C. and Pidgeon, C. (1996) Affinity purification of phospholipase A(2) on immobilized artificial membranes containing and lacking the glycerol backbone. Journal of Chromatography 731, 139-151.
  41. Ong, S.W., Liu, H.L. and Pidgeon, C. (1996) Immobilized artificial membrane chromatography - measurements of membrane partition coefficient and predicting drug membrane permeability. Journal of Chromatography 728, 113-128.
  42. Leone-Bay, A., Ho, K., Agarwal, R., Baughman, R.A., Chaudhary, K., DeMorin, F., Genoble, L., McInnes, C., Lercara, C., et al. (1996) 4-[4-[(2-Hydroxybenzoyl)amino]butyric acid as a novel oral delivery agent for recombinant human growth hormone. J. Med. Chem. 39(13), 2571-2578.
  43. Marcello, J., Eddy, E.P., Smith, P. L., Cheng, H.Y., Mitchell, R.C. and Lee, C.P. (1996) Evaluation of immobilized artificial membrane technology to predict blood brain barrier permeability. Book of Abstracts, 211th ACS National Meeting, New Orleans, La. March 24-28.
  44. Leone-Bay, a., Ho, K.K., Sarubbi, D., Milstein, S., Agarwal, R., McInnes, C., Baughman, R.A., Wang, N.F., Lercara, C., et al. (1996) 4-(4-Salicyloylaminophenyl)butyric acid as a novel oral delivery agent for recombinant human growth hormone. Book of Abstracts, 211th ACS National Meeting, New Orleans, La. March 24-28.
  45. Pidgeon, C. Cai, S.J., Bernal, C. (1996) Mobile phase effects on membrane protein elution during immobilized artificial membrane chromatography. J. Chromatogr. 721(2), 213-30
  46. Abraham, M., Chadha, H.S., Letao, R.A.E., Mitchell, R.C. Lambert, W.J., Kaliszan, R., Nasal, A., Haber, P., (1997) Determination of solute lipophilicity, as log P(octanol and log P(alkane using (styrene-divinylbenzene and immobilized artificial membrane stationary phases in reversed-phase high-performance liquid chromatography. J. Chromatogr. 766(1 + 2), 35-47.
  47. Leone-Bay, A., Paton, D., Freeman, J., Lercara, C., O'Toole, D., Rivera, T., Rosada, C., Harris, E., Baughman, R. (1997) Acylated non- a-amino acids as novel agents for the oral delivery of therapeutic levels of USP heparin. Book of Abstracts, 213th ACS National Meeting, San Francisco, April 13-17.
  48. Salminen, T., Pulli, A., Taskinen, J. (1997) Relationship between immobilized artificial membrane chromatographic retention and the brain penetration of structurally diverse drugs. J. Pharm. Biomed. Anal. 15(4), 469-477.
  49. Barbato, F., La Rotonda, M.I., Quaglia, F. (1997) Interactions of nonsteroidal antiinflammatory drugs with phospholipids: comparison between octanol/buffer partion coefficients and chromatographic indexes on immobilized artificial membranes. J. Pharm. Sci. 86(2), 225-229.
  50. Yang, C.Y., Cai, S.J., Liu, H. Pidgeon, C. (1997) Immobilized artificial membranes - screens for drug-membrane interactions. Adv. Drug Delivery Rev. 23(1-3), 229-256.
  51. Barton, P., Davis, A. M., McCarthy, D. J., Webborn, P. Drug-phospholipid Interactions. 2. Predicting the  Sites of Drug Distribution Using n-Octanol/Water and Membrane/Water Distribution Coefficients. J. Pharm. Sci.  86(9), 1034-1039, (1997).
  52. Wainer, W. I., Johnson, V. D., Wahnon, D., Sotolongo, V. On-line High Performance Liquid Chromatographic  Immobilized Enzyme Reactors for Synthesis of Stereochemically Pure Compounds. Chimica Oggi 15, 45-48,  (1997).
  53. Turowski, M., Kaliszan R. Keratin immobilized on silica as a new stationary phase for chromatographic  modeling of skin permeation. J. Pharm. Biomed. Anal.  15(9-10), 1325-33, (1997).
  54. Liu Hanlan, Cohen David E., Pidgeon Charles. Single Step Purification of Rat Liver Aldolase Using Immobilized  Artificial Membrane Chromatography. J.Chromatogr., B: Biomed. Sci. Appl. 703(1+2), 53-62, (1997).
  55. Zhang, Y., Xiao, Y., Kellar, Wainer, I. Immobilized Nicotinic Receptor Stationary Phase for Online Liquid  Chromatographic Determination of Drug-Receptor Affinities. Analytical Biochemistry 263, Article Number  AB982828, (1998).
  56. Leone-Bay, A., Duncan R. Paton, Freeman, J., Christine Lercara, Doris O’Toole, David Gschneidner, Eric Wang, Elizabeth Harris, Connie Rosado, Theresa Rivera, Aldona DeVincent, Monica Tai, Frank Mercogliano, Rajesh Agarwal,
    Harry Leipold, and Robert A. Baughman (1998) Synthesis and Evaluation of Compounds that Facilitate the Gastrointestinal Absorption of Heparin Journal of Medicinal Chemistry 1998, 41:7, 1163-1171.
  57. Leone-Bay, A.*, Koc-Kan Ho, Rajesh Agarwal, Robert A. Baughman, Kiran Chaudhary, Frenel DeMorin, Lise Genoble, Campbell McInnes, Christine Lercara, Sam Milstein, Doris O'Toole, Donald Sarubbi, Bruce Variano, Duncan R. Paton (1996) 4-[4-(2-Hydroxybenzoyl)aminophenyl]butyric Acid as a Novel Oral Delivery Agent for Recombinant Human Growth HormoneJournal of Medicinal Chemistry, 39, 2571-2578 (1996)
  58. On-line chromatographic analysis of drug­receptor interactions Zhang, Y. and
    Wainer, I.W. American Laboratory, December 1999. 9912
  59. Masucci, John A., Caldwell, Gary W., and Joe P. Foley. A Comparison of the Retention Behavior of b-Blockers Using Immobilized Artificial Membrane Chromatography and Lysophospholipid Micellar Electrokinetic Chromatography, J. Chromatogr. A, 1998, 810, 95-103.
  60. Barbra H. Stewart, Francis Y. Chung, Bradley Tait, C. John Blankley, and O. Helen Chan.  Hydrophobicity of HIV Protease Inhibitors by Immobilized Artificial Membrane Chromatography: Application and Significance to Drug Transport PHARMACEUTICAL RESEARCH, Volume 15, Number 9, September 1998  #980097
  61. Barbato Francesco, Cappello Brunella, Miro Agnese, La Rotonda Maria Immacolata, and Quaglia Fabiana.  Chromatographic Indexes on Immobilzed Artificial Membranes for the Prediction of Transdermal Transport of  Drugs. Farmaco, 53(10,11), 655-661, (1998).
  62. Stewart Barbra H. and Chan O Helen. Use of Immobilzed Artificial Membrane Chromatography for Drug Transport  Applications. J.Pharm. Sci., 87(12), 1471-1478, (1998).
  63. Reichel Andreas and Begley David J. Potential of Immobilized Artificial Membranes for Predicting Drug  Penetration Across the Blood-Brain Barrier. Pharm. Res. 15(8), 1270-1274, (1998).
  64. Ducarme Andre, Neuwels Michel, Goldstein Solo and Massingham Roy. IAM Retention and Blood Brain Barrier  Penetration. Eur. J. Med. Chem., 33(3), 215-223, (1998).
  65. Valko K., Plass, M., Beva, C., Reynolds, D. and Abraham M. H. Relationships Between the Chromatographic  Hydrophobicity and Solute Descriptors Obtained by using several Reversed-phase, Diol, Cyclodextrin and  Immobilized Artificial Membrane-bonded High-performance Liquid Cromatography Columns. J. Chromatogr.,  A, 797(1+2), 41-55, (1998).
  66. Caldwell Gary W., Masucci John A., Evangelisto Mary and White Robert. Evaluation of the Immobilized Artificial  Membrane Phosphatidylcholine. Drug Discovery Column for High-performance Liquid Chromatographic Screening  of Drug-membrane Interactions. J. Chromatogr., A. 800(2), 161-169, (1998).
  67. Ottiger C, Wunderli-Allenspach H,  Immobilized artificial membrane (IAM)-HPLC 
    for partition studies of neutral and ionized acids and bases in comparison with
    the liposomal partition system. PHARMACEUTICAL RESEARCH ,16: (5) 643-650 MAY 1999
  68. Demare S., Roy D and Legendre J. Y. Factors Gonerning the Retention of Solutes on Chromatographic Immobilized  Artificial Membranes: Application to Anti-inflammotory and Analgesic Drugs. J. Liq. Chromatogr. Relat. Technol.,  22(17), 2675-2688, (1999).
  69. Valko Klara, Du Chau My, Christopher D, Reynolds, Derek P. and Abraham Michael H. Rapid-Gradient HPLC  Method for Measuring Drug Interactions with Immobilized Artificial Membrane: Comparison with Other  Lipophilicity Measures. J. Pharm. Sci., 89(8), 1085-1096, (2000).
  70. Kepczynska Elzbieta, Bojarski Jacek, Haber Piotr and Kaliszan Roman. Retention of Barbituric Acid Derivatives  on Immobilized Artificial Membrane Stationary Phase and its Correlation with Biological Activity. Biomed.  Chromatogr., 14(4), 256-260, (2000).
  71. Escuder Gilabert L., Sagrado S., Villanueva Camanas R. M. and Medina Hernandez M. J. Development of  Predictive Retention-activity Relationships Models of Non-steroidal Anti-inflammatory Drugs by Micellar Liquid  Chromatography: Comparison with Immobilized Artificial Membrane Columns. J. Chromatogr., B: Biomed. Sci.  Appl., 740(1), 59-70, (2000).
  72. Amato, Marzia, Francesco Barbato,* Patrizia Morrica, Fabiana Quaglia, Maria I. La Rotonda Interactions between Amines and Phospholipids: A Chromatographic Study on Immobilized Artificial Membrane (IAM) Stationary Phases at Various pH Values, Helvetica Chimica Acta, No. 10,  2000
  73. Lili Lu, Fabio Leonessa, Robert Clarke, and Irving W. Wainer Competitive and Allosteric Interactions in Ligand Binding to P-glycoprotein as Observed on an Immobilized P-glycoprotein Liquid Chromatographic Stationary Phase  Mol Pharmacol Vol. 59, Issue 1, 62-68, (2001)
  74. I.J. Hidalgo, Assessing the Absorption of New Pharmaceuticals Current Topics in Medicinal Chemistry, Volume 1, Number 5, 2001Pp.385-401
  75. Agnes Taillardat-Bertschinger, Pierre-Alain Carrupt, Francesco Barbato and Bernard Testa
    "Immobilized Artificial Membrane HPLC in Drug Research",
    Journal of Medicinal Chemistry, 46(5), 654-665, Feb, (2003).
  76. El-Gendy, Ahmed M., Adejere, Adeboyeh, Membrane Permeability Related Physiochemical Properties of a Novel gamma-Secretase Inhibitor., International Journal of Pharmaceutics, 280(1-2), 47-55. (2004)
  77. Barbato, F., diMartino, G., Grumetto, L., La Rotondo, M.I., Prediction of Drug-Membrane Interactions by IAM-HPLC, Effects of Different Phospholipid Stationary Phases on the Partition of Bases., European Journal of Pharmaceutical Sciences, 22(4), 261-269. (2004)
  78. Markoglou,Nektaria; Hsuesh, Ruth; Wainer, Irving. Immobilized Enzyme Reactors Based Upon the Flavoenzymes Monoamine Oxidase A and B . Journal of Chromatography, B: Analytical Technologies in the Biomedical and Life Sciences, 804(2), 295-302. (2004)
  79. Beigi, Farideh; Wainer, Irving;. Syntheis of Immobilized G Protein-Coupled Receptor Chromatographic Stationary Phases: Characterization of Immobilized : and k Opioid Receptors. Anal. Chem, 75, 4480-4485, (2003)
  80. Jozwiak, Krzysztof; Ravichandran, Sarangan; Collins, Jack; Wanier, Irving Interaction of Noncompetitive Inhibitors with an Immobilized en "3$4 Nicotinic Acetylcholine Receptor Investigated by Affinity Chromatography, Quantitative-Structure Activity Relationship Analysis, and Molecular Docking. J. Med. Chem. 47, 4008-4021, (2004)
  81. Moaddel, R; Yamaguchi, R; Ho, P.C.; Patel, S.; Hsu, C.P.; Subrahmanyam, V.; Wainer, I.W.; Development and Characterization of an Immobilized Human Organic Transporter Based Liquid Chromatographic Stationary Phase.. Journal of Chromatography B, (Available online at www.sciencedirect.com), (2005)
  82. Valko, K. Application of high-performance liquid chromatography based measurements of lipophilicity to model biological distribution. J. Chromatogr. A. 1037, (1-2), 299-310 (2004)
  83. Fabienne Péhourcq, Myriam Matoga, Bernard Bannwarth Diffusion of arylpropionate non-steroidal anti-inflammatory drugs into the cerebrospinal fluid: a quantitative structure activity relationship approach. Fundamental & Clinical Pharmacology. Volume 18: Issue 1 (2004)
  84. Yen, T.E., Agatonovic-Kustrin, S., Evans, A.M., Nation, R.L., Ryand, J., Prediction of drug absorption based on immobilized artificial membrane (IAM) chromatography separation and calculated molecular descriptors
    Journal of Pharmaceutical and Biomedical Analysis. Vol. 38, No. 3, pages 472-478 (2005) DOI: 10.1016/j.jpba.2005.01.040
  85. D. Vrakas, D. Hadjipavlou-Litina, A.Tsantili-Kakoulidou, Retention of substituted coumarins using Immobilized Artificial Membrane (IAM) Chromatography: A comparative study with n-Octanol Partitioning and Reversed-Phase HPLC and TLC, J. Pharm.Biomed. Anal. 39, 908-913 (2005)
  86. The use of immobilized artificial membrane (IAM) chromatography for determination of lipophilicity. Barbato, Francesco. Dipartimento di Chimica Farmaceutica e Tossicologica, Universita degli Studi di Napoli Federico II, Naples, Italy. Current Computer-Aided Drug Design (2006), 2(4), 341-352.
  87. Quantitative structure-retention relationship studies using immobilized artificial membrane chromatography I: Amended linear solvation energy relationships with the introduction of a molecular electronic factor. Li, Jie; Sun, Jin; Cui, Shengmiao; He, Zhonggui. Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Peop. Rep. China. Journal of Chromatography, A (2006), 1132(1-2), 174-182.
  88. Method for measuring orally administered drug absorption into intestine through measuring retention time of drug in immobilized artificial membrane phosphatidylcholine column and method for measuring brain penetration of drug using the same. Yoo, Sun Dong; Shin, Beom Soo; Yun, Chi Ho. (S. Korea). Repub. Korean Kongkae Taeho Kongbo (2006)
  89. Chromatographic Estimation of Drug Disposition Properties by Means of Immobilized Artificial Membranes (IAM) and C18 Columns. Lazaro, Elisabet; Rafols, Clara; Abraham, Michael H.; Roses, Marti. Departament de Quimica Analitica, Universitat de Barcelona, Barcelona, Spain. Journal of Medicinal Chemistry (2006), 49(16), 4861-4870.
  90. Different retention behavior of structurally diverse basic and neutral drugs in immobilized artificial membrane and reversed-phase high performance liquid chromatography: Comparison with octanol-water partitioning. Vrakas, Demetris; Giaginis, Costas; Tsantili-Kakoulidou, Anna. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Athens, Greece. Journal of Chromatography, A (2006), 1116(1-2), 158-164. Abstract
  91. Molecular lipophilicity determination of a huperzine series by HPLC: Comparison of C18 and IAM stationary phases. Darrouzain, Francois; Dallet, Philippe; Dubost, Jean-Pierre; Ismaili, Lhassane; Pehourcq, Fabienne; Bannwarth, Bernard; Matoga, Myriam; Guillaume, Yves C. Equipe des Sciences Separatives et Biopharmaceutiques (2SB, EA/3924), Laboratoire de Chimie Analytique et de Chimie Therapeutique, Faculte de Medecine et de Pharmacie, Besancon, Fr. Journal of Pharmaceutical and Biomedical Analysis (2006), 41(1), 228-232.
  92. Rapid screening of blood-brain barrier penetration of drugs using the immobilized artificial membrane phosphatidylcholine column chromatography. Yoon, Chi Ho; Kim, Soo Jin; Shin, Beom Soo; Lee, Kang Choon; Yoo, Sun dong. College of Pharmacy, Sungkyunkwan University, Gyeonggi-do, S. Korea. Journal of Biomolecular Screening (2006), 11(1), 13-20.
  93. Immobilized artificial membrane chromatography: A useful tool for predicting membrane permeability. Adejare, Adeboye; El-Gendy, Ahmed. Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA, USA. Abstracts of Papers, 231st ACS National Meeting, Atlanta, GA, United States, March 26-30, 2006 (2006), MEDI-211.
  94. Thermodynamic partitioning behavior for solutes into immobilized artificial membrane or an n-octanol/water system. Sun, Jin; Zhang, Tian-Hong; Li, Jie; Mao, Jing-Jing; He, Zhong-Gui. Dep. Biopharmaceutics, Sch. Pharmacy, Shenyang Pharmaceutical Univ., Shenyang, Peop. Rep. China. Gaodeng Xuexiao Huaxue Xuebao (2006), 27(2), 349-351.
  95. A comparative study of void volume markers in immobilized-artificial-membrane and reversed-phase liquid chromatography. Luo, Haibin; Cheng, Yuen-Kit. Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong. Journal of Chromatography, A (2006), 1103(2), 356-361.
  96. Profiling drug membrane transport via immobilized artificial membrane chromatography. Sun, Jin; Zhang, Tian-Hong; He, Zhong-Gui. Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Peop. Rep. China. Current Pharmaceutical Analysis (2005), 1(3), 273-282. Abstract
  97. Retention of substituted coumarins using immobilized artificial membrane (IAM) chromatography: A comparative study with n-octanol partitioning and reversed-phase HPLC and TLC. Vrakas, Demetris; Hadjipavlou-Litina, Dimitra; Tsantili-Kakoulidou, Anna. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Athens, Greece. Journal of Pharmaceutical and Biomedical Analysis (2005), 39(5), 908-913. Publisher: Elsevier B.V., CODEN: JPBADA ISSN: 0731-7085. Journal written in English. CAN 144:27763 AN 2005:1112505 CAPLUS (Copyright (C) 2006 ACS on SciFinder (R))
  98. Immobilized artificial membrane chromatography and its application in profiling the drug membrane transport. Sun, Jin; Zhang, Tianhong; He, Zhonggui. Department of Biopharmaceutics, School of Pharmacy, Shenyang Phaaeutical University, Shenyang, Peop. Rep. China. Sepu (2005), 23(4), 378-383.
  99. Characterization of immobilized artificial membrane (IAM) and XTerra columns by means of chromatographic models. Lazaro, Elisabet; Rafols, Clara; Roses, Marti. Departament de Quimica Analitica, Universitat de Barcelona, Barcelona, Spain. Journal of Chromatography, A (2005), 1081(2), 163-173.
  100. Modeling Caco-2 permeability of drugs using immobilized artificial membrane chromatography and physicochemical descriptors. Chan, E. C. Y.; Tan, W. L.; Ho, P. C.; Fang, L. J. The Capricorn, S*BIO Pte Ltd., Singapore, Singapore. Journal of Chromatography, A (2005), 1072(2), 159-168.
  101. In vitro method for determining drug permeability using immobilized artificial membrane chromatography. Guo, Junan; He, Ping; Qu, Anthony Yi; Yang, Steve Yong-tao; Anik, Shabbir. (Can.). U.S. Pat. Appl. Publ. (2005),
  102. Immobilised artificial membrane chromatography coupled with molecular probing: Mimetic system for studying lipid-calcium interactions in nutritional mixtures. Hernando, Vanessa; Rieutord, Andre; Pansu, Robert; Brion, Francoise; Prognon, Patrice. Groupe de Chimie Analytique de Paris Sud, EA 3343, Laboratoire de Chimie Analytique, Faculte de Pharmacie, Chatenay-Malabry, Fr. Journal of Chromatography, A (2005), 1064(1), 75-84. retention. Consequently, it was demonstrated that IAM appears as a suitable model to get a better insight on the lipid-calcium interactions taking place in nutritional mixts.

DEACTIVATED HYDROCARBONACEOUS SILICA AND IMMOBILIZED ARTIFICIAL MEMBRANE STATIONARY PHASES IN HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF HYDROPHOBICITIES OF ORGANIC-BASES : RELATIONSHIP TO LOG-P AND CLOGP

KALISZAN R, KALISZAN A, WAINER IW

MCGILL UNIV,MONTREAL GEN HOSP,DEPT ONCOL,ROOM B7113,1650 CEDAR AVE MONTREAL H3G 1A4 QUEBEC

Retention parameters for a series of 29 organic base drugs (including 17 phenothiazine derivatives) were measured by reversed-phase high-performance liquid chromatography (HPLC) employing new columns of distinctive partition properties. One column was a deactivated alkyl-bonded silica and two others were packed with lecithin bonded propylamino-silica, i.e. the immobilized artificial membrane (IAM) columns; one of the IAM stationary phases had the unreacted propylamine moieties additionally end-capped with methylglycolate. The highly deactivated hydrocarbonaceous silica column showed regular rectilinear relationships between logarithms of chromatographic capacity factors and the content of organic modifier in aqueous eluent; it is suitable for generating a chromatographic scale of hydrophobicity. Such a scale (hydrocarbonaceous) is different from that provided by measurement of partitioning of solutes between n-octanol and water (alkanol log P scale). The relative hydrophobicity parameters determined by HPLC on the IAM columns were different from both log P scale and from the hydrocarbonaceous chromatographic hydrophobicity scale. The hydrophobicity parameter, CLOGP, theoretically calculated by the fragmental methods, correlated better than log P with chromatographic hydrophobicity parameters. It has been postulated that each hydrophobicity measuring system reveals some specific aspects of the hydrophobicity phenomenon and that the nature of hydrophobic binding sites on receptors and plasma proteins may require different hydrophobicity models than drug permeation through biological membranes. By means of HPLC, diverse hydrophobicity measures can readily be determined, among which those most suitable for specific QSAR applications can be identified.

Keywords HYDROPHOBICITY; LOG-P; CLOGP; CHROMATOGRAPHIC HYDROPHOBICITY
PARAMETERS; DEACTIVATED HYDROCARBONACEOUS SILICA STATIONARY PHASE; IMMOBILIZED ARTIFICIAL MEMBRANE STATIONARY PHASES; PARTITION-COEFFICIENTS; REVERSED-PHASE; OCTANOL; WATER; HPLC

Catagories PHARMACOLOGY & PHARMACY

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,v. 11(#6),1993,505-511.
 

 Marzia Amato, Francesco Barbato,* Patrizia Morrica, Fabiana Quaglia, Maria I. La Rotonda Interactions between Amines and Phospholipids: A Chromatographic Study on Immobilized Artificial Membrane (IAM) Stationary Phases at Various pH Values

The chromatographic capacity factors (log k') for 23 amines were measured by High Performance Liquid Chromatography (HPLC) on a stationary phase composed of phospholipids, the so-called 'Immobilized Artificial Membrane' (IAM). The chromatographic behaviour of the compounds, which consist of primary, secondary, and tertiary amines, and compounds with endocyclic amino functions,was studied with eluents at various pH values (7.0, 5.5, and 3.0). The results were compared both to the octanol/buffer partition values of neutral forms (log P) and to those of mixtures of neutral and ionised forms, existing at the three pH values above mentioned (log D7.0, log D5.5, and log D3.0). At pH 7.0, the log k' of all secondary and tertiary amines overlapped with those previously observed for neutral isolipophilic compounds. This behaviour was also observed for primary amines, but only for compounds fully ionised at this pH. In contrast, the partially ionised primary amines at pH 7.0 and the compounds with an endocyclic amino function both showed stronger interactions with phospholipids than expected on the basis of log P. The changes in retention observed with eluents at pH 5.5 indicated that retention varies with the ionisation degree of the analytes. At pH 3.0, the interaction between phospholipids and the ionised forms of the amines considered was impaired probably by a change in the charges on the IAM surface. The present study indicates that phospholipids are a partitioning phase  that better accommodates the neutral forms of primary amines than does octanol. Moreover, the phospholipid phase is much less sensitive to the ionisation of analytes than octanol, but only at pH 7.0 and 5.5; indeed, the ionised forms of all the amines considered are retained to the same extent as expected for hypothetical neutral isolipophilic compounds. We can thus conclude that, for amines, the partition scale in phospholipids is distinct from the one in octanol. Helvetica Chimica Acta, No. 10,  2000, 2836-2847

 Immobilized artificial membrane (IAM)-HPLC for partition studies of neutral and ionized acids and bases in comparison with the liposomal partition system

Purpose. To study the partitioning of model acids ((RS)-warfarin and salicylic acid), and bases (lidocaine, (RS)-propranolol and diazepam), with immobilized artificial membrane (IAM)-HPLC, as compared to partitioning in the standardized phosphatidylcholine liposome/buffer system.

Methods. The pH-dependent apparent partition coefficients D were calculated from capacity factors (k(IAM)') obtained by IAM-HPLC, using a 11-carboxylundecylphosphocholine column. For lipophilic compounds k(IAM)', values were determined with organic modifiers and extrapolation to 100% water phase (k(IAMw)') was optimized. Temperature dependence was explored (23 to 45 degrees C), and Gibbs free energy (Delta G), partial molar enthalpy (Delta H) and change in entropy (Delta S) were calculated. Equilibrium dialysis was used for the partitioning studies with the liposome/buffer system.

Results. For extrapolation of k(IAMw)', linear plots were obtained both with the respective dielectric constants and the mole fractions of the organic modifier. All tested compounds showed a similar pH-D diagram in both systems; however, significant differences were reproducibly found in the pH range of 5 to 8. In all cases, Delta G and Delta H were negative, whereas Delta S values were negative for acids and positive for bases.

Conclusions. In both partitioning systems, D values decreased significantly with the change from the neutral to the charged ionization state of the solute. The differences found under physiological conditions, i.e. around pH 7.4, were attributed to nonspecific interactions of the drug with the silica surface of the IAM column.

 
Competitive and Allosteric Interactions in Ligand Binding to P-glycoprotein as Observed on an Immobilized P-glycoprotein Liquid Chromatographic Stationary Phase

Lili Lu, Fabio Leonessa, Robert Clarke, and Irving W. Wainer Department of Pharmacology and the Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC

A liquid chromatographic stationary phase containing immobilized P-glycoprotein (Pgp) was synthesized using cell membranes obtained from Pgp-expressing cells. The resulting Pgp-stationary phase was used in frontal and zonal chromatographic studies to investigate the binding of vinblastine (VBL), doxorubicin (DOX), verapamil (VER), and cyclosporin A (CsA) to the immobilized Pgp. The compounds were added individually to the chromatographic system with or without ATP in the running buffer. Using this approach, dissociation constants were calculated for VBL (23.5 ± 7.8 nM), DOX (15.0 ± 3.2 µM), VER (54.2 ± 4.7 µM), and CsA [97.9 ± 19.4 nM (without ATP) and 62.5 ± 4.6 nM (with ATP)]. The compounds were also added in pairs using standard competitive chromatography procedures. The results of the study demonstrate that competitive interactions occurred between VBL and DOX, cooperative allosteric interactions occurred between VBL and CsA and ATP and CsA, and anticooperative allosteric interactions occurred between ATP and VBL and VER. The chromatographic studies indicate that the immobilized Pgp was modified by ligand and cofactor binding and that the stationary phase can be used to study drug-drug binding interactions on the Pgp molecule.

 Assessing the Absorption of New Pharmaceuticals
I.J. Hidalgo

The advent of more efficient methods to synthesize and screen new chemical compounds is increasing the number of chemical leads identified in the drug discovery phase. Compounds with good biological activity may fail to become drugs due to insufficient oral absorption. Selection of drug development candidates with adequate absorption characteristics should increase the probability of success in the development phase. To assess the absorption potential of new chemical entities numerous in vitro and in vivo model systems have been used. Many laboratories rely on cell culture models of intestinal permeability such as, Caco-2, HT-29 and MDCK. To attempt to increase the throughput of permeability measurements, several physicochemical methods such as, immobilized artificial membrane (IAM) columns and parallel artificial membrane permeation assay (PAMPA) have been used. More recently, much attention has been given to the development of computational methods to predict drug absorption. However, it is clear that no single method will sufficient for studying drug absorption, but most likely a combination of systems will be needed. Higher throughput, less reliable methods could be used to discover ?loser? compounds, whereas lower throughput, more accurate methods could be used to optimize the absorption properties of lead compounds. Finally, accurate methods are needed to understand absorption mechanisms (efflux ?limited absorption, carrier-mediated, intestinal metabolism) that may limit intestinal drug absorption. This information could be extremely valuable to medicinal chemists in the selection of favorable chemo-types. This review describes different techniques used for evaluating drug absorption and indicates their advantages and disadvantages.

 Immobilized Artificial Membrane (IAM)-HPLC in Drug Research
Agnes Taillardat-Bertschinger1, Pierre-Alain Carrupt1, Francesco Barbato2 and Bernard Testa1*

  1. Institut de Chimie Thérapeutique, Section de Pharmacie, Université de Lausanne, CH-1015 Lausanne, Switzerland
  2. Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, I-80131 Naples, Italy

Content Abstract

  1. Background: Drug permeation and lipophilicity
  2. Structural features of single- and double-chain IAMs
  3. Capacity factors as a measure of partitioning in IAMs
  4. Column stability and silanophilic interactions
  5. Structural comparison between IAMs and liposomes
  6. Predictive value of IAM capacity factors
    1. Relations between IAM capacity factors and other lipophilicity parameters
    2. Relations of IAM capacity factors with drug permeation and pharmacokinetic behavior
  7. Conclusion

Abstract - Application of high-performance liquid...
Immobilized artificial membranes (IAMs) are of particular interest to obtain informative lipophilicity parameters, since they combine the speed of HPLC with the biochemical relevance of liposomes. In this review, various aspects of IAM-HPLC are presented and critically discussed. First, single- and double-chain IAMs are compared and some advantages outlined. The key step of transforming capacity factors into lipophilicity indices useable in quantitative structure-permeability relationships (QSPRs) is then described. This is followed by a discussion of technical problems such as column stability and silanophilic interactions. The next section compares the characteristics of IAMs and liposomes, showing that a number of structural differences indeed exist. In the last and most important section, a number of recent publications are used to evaluate the structural information encoded in IAM capacity factors and their relationship with membrane permeation. First, it is shown that the IAM capacity factors encode different balances of recognition forces depending on the neutral or ionized nature of the analytes. Whereas the capacity factors of neutral compounds are usually well related to lipophilicity determined in isotropic solvent systems, ionic interactions dominate the retention of ionized solutes. Thus, cationic drugs show a marked affinity for IAMs due to an attractive ionic bond, whereas anions tend to show the opposite effect. A number of studies also document relations between IAM capacity factors and passive membrane permeation (e.g., intestinal and cutaneous). However, no study has yet been able to show which lipophilicity descriptor (IAM capacity factors, n-octanol/water or liposomes/water partitioning) is best suited to predict the membrane permeability of large series of compounds. It seems that the answer differs according to the set of compounds under investigation.

 Abstract - Application of high-performance liquid chromatography based measurements of lipophilicity to model biological distribution
Octanol-water partition coefficients are the most widely used measure of lipophilicity in modelling biological partition/distribution. It has long been recognised that the retention of a compound in reversed-phase liquid chromatography is governed by its lipophilicity/hydrophobicity, and thus shows correlation with an octanol-water partition coefficient. A great number of publications have reported the efforts made to adjust HPLC conditions to measure surrogate octanol-water partition coefficients. However, there is no general consensus in this field. HPLC provides a platform to measure various types of lipophilicity that can provide relevant information about the compounds' property. In this way HPLC can be more valuable than just a surrogate for octanol-water partition. Chromatography using biomimetic stationary phases may provide better insight for biological partition/distribution processes. The research in this field is still ongoing and a large variety of HPLC conditions have been suggested. This review will outline approaches to overcoming the difficulties of standardisation and describe different theoretical approaches for comparison of HPLC lipophilicity data obtained under various conditions, along with the relation of these results to biological partition/distribution.

 Abstract - Prediction of drug absorption
The aim of this study was to evaluate the usefulness of IAM chromatography in building a model that would allow prediction of drug absorption in humans. The human intestinal absorption values (%HIA) for 52 drugs with low to high intestinal absorption were collected from the literature. The retention (capacity factor, k′) of each drug was measured by reverse-phase HPLC using an IAM.PC.DD2 column (prepared with phosphatidylcholine analogs, 12 μM, 300 Å, 15 cm × 4.6 mm) with an eluent of acetonitrile–0.1 M phosphate buffer at pH 5.4. In addition, 76 molecular descriptors and solubility parameters for each drug were calculated using ChemSW from the 3D-molecular structures. Stepwise regression was employed to develop a regression equation that would correlate %HIA with molecular descriptors and k

Human intestinal absorption was reciprocally correlated to the negative value of the capacity factor (−1/k′) (R = 0.64). The correlation was further improved with the addition of molecular descriptors representing molecular size and shape (molecular width, length and depth) solubility (solubility parameter, HLB, hydrophilic surface area) and polarity (dipole, polar surface area) (R = 0.83).

Experimentally measured IAM chromatography retention values and calculated molecular descriptors and solubility parameters can be used to predict intestinal absorption of drugs in humans. Developed QSAR can be used as a screening method in the designing of drugs with appropriate IA and for the selection of drug candidates in the early stage of drug discovery process.

Diffusion of arylpropionate
A quantitative structure-activity relationship (QSAR) analysis of a series of arylpropionic acid non-steroidal anti-inflammatory drugs (NSAIDs) has been performed to determine which physicochemical properties of these compounds are involved in their diffusion into the cerebrospinal fluid (CSF). The penetration of eight arylpropionic acid derivatives into CSF was studied in male Wistar rats. After intraperitoneal administration of each compound (5 mg/kg), blood and CSF samples were collected at different times (0.5, 1, 3 and 6 h). The fraction unbound to plasma protein was determined using ultrafiltration. The areas under the curve of the free plasma (AUCF) and CSF (AUCCSF) concentrations were calculated according to the trapezoidal rule. The overall drug transit into CSF was estimated by the ratio RAUC (AUCCSF : AUCF). The lipophilicity was expressed as the chromatographic capacity factor (log kIAM) determined by high-performance liquid chromatography on an immobilized artificial membrane (IAM) column. A significant parabolic relationship was sought between lipophilicity (log kIAM) and the capacity of diffusion across the blood-brain barrier (log RAUC) (r = 0.928; P < 0.01). The arylpropionic acid NSAIDs exhibiting a lipophilicity value between 1.1 and 1.7 entered the CSF easily (RAUC > 1). The molecular weight (MW) was included in this parabolic relationship by means of a multiple regression analysis. This physicochemical parameter improved the correlation (r = 0.976; P < 0.005). Based on our findings, diffusion of arylpropionic acid NSAIDs into CSF appears to depend primarily on their lipophilicity and MW.