Analytical and Bioanalytical Chemistry

, Volume 394, Issue 3, pp 707–729 | Cite as

Analytical tools for the physicochemical profiling of drug candidates to predict absorption/distribution

  • Yveline Henchoz
  • Bruno Bard
  • Davy Guillarme
  • Pierre-Alain Carrupt
  • Jean-Luc Veuthey
  • Sophie MartelEmail author


The measurement of physicochemical properties at an early phase of drug discovery and development is crucial to reduce attrition rates due to poor biopharmaceutical properties. Among these properties, ionization, lipophilicity, solubility and permeability are mandatory to predict the pharmacokinetic behavior of NCEs (new chemical entities). Due to the high number of NCEs, the analytical tools used to measure these properties are automated and progressively adapted to high-throughput technologies. The present review is dedicated to experimental methods applied in the early drug discovery process for the determination of solubility, ionization constants, lipophilicity and permeability of small molecules. The principles and experimental conditions of the different methods are described, and important enhancements in terms of throughput are highlighted.


Scheme of the Drug Research Process.


Physicochemical profiling Solubility Ionization constant Lipophilicity Permeability Experimental models 





Absorption, distribution, metabolism and elimination


Absorption, distribution, metabolism, elimination and toxicity


Atmospheric pressure chemical ionization


Atmospheric pressure ionization


Atmospheric pressure photoionization


Gradient steepness


Blood–brain barrier


Corona aerosol discharge


3-(Cyclohexylamino)-1-propanesulfonic acid


Contactless conductivity detection


Capillary electrophoresis


Central nervous system


Compounds crossing the blood–brain barrier


Compounds not transported into the brain


Capillary zone electrophoresis


Diode array detector


Dimethyl ether


Dimethyl sulfoxide


Evaporating light scattering detector


Electroosmotic flow


Electrospray ionization


Fasted state simulated intestinal fluid


Fed state simulated intestinal fluid


4-(2-Hydroxyethyl)piperazine-1-propanesulfonic acid


Hydrophilic interaction liquid chromatography


High-performance liquid chromatography


High-throughput screening


Immobilized artificial membrane


Interface between two immiscible electrolyte solutions


Retention factor


Retention factor at the initial gradient composition


Liquid chromatography


Effective length of the capillary


Liposome electrokinetic chromatography

log DpH

Logarithm of the distribution coefficient at a given pH

log kIAM

Logarithm of the retention factor measured on immobilized artificial membrane columns

log kw

Logarithm of the retention factor extrapolated to 100% water

log P

Logarithm of the partition coefficient

log Pa

Apparent permeability coefficient

log Pe

Effective permeability coefficient

log PI

Logarithm of the partition coefficient of an ion

log Plip

Logarithm of the partition coefficient in liposomes/water system

log Poct

Logarithm of the partition coefficient in the 1-octanol/water system


Limit of quantification


Linear solvation free-energy relationship


Linear solvent strength


Total length of the capillary


Lyophilized solubility assay


Microemulsion electrokinetic chromatography


Micellar electrokinetic chromatography




2-Morpholinoethanesulfonic acid


Mass spectrometry


New chemical entity


Nuclear magnetic resonance


Nano-quantity analyte detector


Octadecyl-bonded silica


Pressure-assisted capillary electrophoresis


Parallel artificial membrane permeability assay






Poly(diallyldimethylammonium chloride)




Ionization constant

\({\text{p}}K^{{{\text{app}}}}_{{\text{a}}} \)

Apparent ionization constant


Polyvinylidene fluoride




Refractive index


Reversed-phase liquid chromatography


Structure–activity relationship


Sodium dodecyl sulfate


Column dead time


System dwell time


Migration time of the electroosmotic flow marker


Gradient time


Migration time


Migration time of the micelle marker


Migration time of the EOF marker


Retention time of a compound




Ultrahigh-pressure liquid chromatography


Vesicle electrokinetic chromatography




Change in composition of the mobile phase during the gradient


Effective mobility


  1. 1.
    Kennedy T (1997) Drug Discov Today 2:436–444CrossRefGoogle Scholar
  2. 2.
    Testa B, van de Waterbeemd H, Folkers G, Guy R (eds)(2001) Pharmacokinetic optimization in drug research: biological, physicochemical and computational strategies. Wiley-VHCA, ZurichGoogle Scholar
  3. 3.
    Smith DA, Jones BC, Walker DK (1996) Med Res Rev 16:243–266PubMedCrossRefGoogle Scholar
  4. 4.
    Kerns EH (2001) J Pharm Sci 90:1838–1858PubMedCrossRefGoogle Scholar
  5. 5.
    Alsenz J, Kansy M (2007) Adv Drug Deliv Rev 59:546–567PubMedCrossRefGoogle Scholar
  6. 6.
    Testa B, Krämer SD, Wunderli-Allenspach H, Folkers G (eds)(2006) Pharmacokinetic profiling in drug research. Biological, physicochemical, and computational strategies. Verlag Hevetica Chimica Acta; Wiley-VCH, ZürichGoogle Scholar
  7. 7.
    Avdeef A (2003) Absorption and drug development. Wiley, HobokenGoogle Scholar
  8. 8.
    Avdeef A, Comer JEA, Thomson SJ (1993) Anal Chem 65:42–49CrossRefGoogle Scholar
  9. 9.
    Takacs-Novak K, Box KJ, Avdeef A (1997) Int J Pharm 151:235–248CrossRefGoogle Scholar
  10. 10.
    Avdeef A, Box KJ, Comer JEA, Gilges M, Hadley M, Hibbert C, Patterson W, Tam KY (1999) J Pharm Biomed Anal 20:631–641PubMedCrossRefGoogle Scholar
  11. 11.
    Mannhold R (2008) Molecular drug properties. Wiley-VCH, WeinheimGoogle Scholar
  12. 12.
    Morgan ME, Liu K, Anderson BD (1998) J Pharm Sci 87:238–245PubMedCrossRefGoogle Scholar
  13. 13.
    Kristl A (2009) Drug Dev Ind Pharm 35:114–117PubMedCrossRefGoogle Scholar
  14. 14.
    Tosco P, Rolando B, Fruttero R, Henchoz Y, Martel S, Carrupt PA, Gasco A (2008) Helv Chim Acta 91:468–482CrossRefGoogle Scholar
  15. 15.
    Allen RL, Box KJ, Comer JEA, Peake C, Tam KY (1998) J Pharm Biomed Anal 17:699–712PubMedCrossRefGoogle Scholar
  16. 16.
    Tam KY, Takacs-Novak K (1999) Pharm Res 16:374–381PubMedCrossRefGoogle Scholar
  17. 17.
    Mitchell RC, Salter CJ, Tam KY (1999) J Pharm Biomed Anal 20:289–295PubMedCrossRefGoogle Scholar
  18. 18.
    Takacs-Novak K, Tam KY (2000) J Pharm Biomed Anal 21:1171–1182PubMedCrossRefGoogle Scholar
  19. 19.
    Tam KY, Takacs-Novak K (2001) Anal Chim Acta 434:157–167CrossRefGoogle Scholar
  20. 20.
    Box K, Bevan C, Comer J, Hill A, Allen R, Reynolds D (2003) Anal Chem 75:883–892PubMedCrossRefGoogle Scholar
  21. 21.
    Alibrandi G, Coppolino S, Micall N, Villari A (2001) J Pharm Sci 90:270–274PubMedCrossRefGoogle Scholar
  22. 22.
    Avdeef A, Testa B (2002) Cell Mol Life Sci 59:1681–1689PubMedCrossRefGoogle Scholar
  23. 23.
    Pang S, Kenseth J, Coldiron S (2004) Drug Discov Today 9:1072–1080PubMedCrossRefGoogle Scholar
  24. 24.
    Poole SK, Patel S, Dehring K, Workman H, Poole CF (2004) J Chromatogr 1037:445–454CrossRefGoogle Scholar
  25. 25.
    Jia Z (2005) Curr Pharm Anal 1:41–56CrossRefGoogle Scholar
  26. 26.
    Wan H, Thompson RA (2005) Drug Discov Today Technol 2:171–178Google Scholar
  27. 27.
    Wan H, Ulander J (2006) Expert Opin Drug Metab Toxicol 2:139–155PubMedCrossRefGoogle Scholar
  28. 28.
    Babic S, Horvat AJM, Pavlovic DM, Kastelan-Macan M (2007) Trends Anal Chem 26:1043–1061CrossRefGoogle Scholar
  29. 29.
    Krishna MV, Srinath M, Sankar DG (2008) Curr Trends Biotechnol Pharm 2:142–155Google Scholar
  30. 30.
    Henchoz Y, Schappler J, Geiser L, Prat J, Carrupt PA, Veuthey JL (2007) Anal Bioanal Chem 389:1869–1878PubMedCrossRefGoogle Scholar
  31. 31.
    Fuguet E, Reta M, Gibert C, Roses M, Bosch E, Rafols C (2008) Electrophoresis 29:2841–2851PubMedGoogle Scholar
  32. 32.
    Liskova A, Krivankova L (2005) Electrophoresis 26:4429–4439PubMedCrossRefGoogle Scholar
  33. 33.
    de Nogales V, Ruiz R, Roses M, Rafols C, Bosch E (2006) J Chromatogr A 1123:113–120PubMedCrossRefGoogle Scholar
  34. 34.
    Plasson R, Cottet H (2006) Anal Chem 78:5394–5402PubMedCrossRefGoogle Scholar
  35. 35.
    Slampova A, Krivankova L, Gebauer P, Bocek P (2008) J Chromatogr A (in press)Google Scholar
  36. 36.
    Vcelakova K, Zuskova I, Kenndler E, Gas B (2004) Electrophoresis 25:309–317PubMedCrossRefGoogle Scholar
  37. 37.
    Zuskova I, Novotna A, Vcelakova K, Gas B (2006) J Chromatogr B 841:129–134Google Scholar
  38. 38.
    Smith CS, Khaledi MG (1993) Anal Chem 65:193–198PubMedCrossRefGoogle Scholar
  39. 39.
    Reijenga JC, Gagliardi LG, Kenndler E (2007) J Chromatogr A 1155:142–145PubMedCrossRefGoogle Scholar
  40. 40.
    Ishihama Y, Oda Y, Asakawa N (1994) J Pharm Sci 83:1500–1507PubMedCrossRefGoogle Scholar
  41. 41.
    Ehala S, Misek J, Stara IG, Stary I, Kasicka V (2008) J Sep Sci 31:2686–2693PubMedCrossRefGoogle Scholar
  42. 42.
    Bellini S, Uhrova M, Deyl Z (1997) J Chromatogr 772:91–101CrossRefGoogle Scholar
  43. 43.
    Castagnola M, Rossetti DV, Misiti F, Cassiano L, Giardina B, Messana I (1997) J Chromatogr 792:57–65CrossRefGoogle Scholar
  44. 44.
    Barron D, Irles A, Barbosa J (2000) J Chromatogr 871:367–380CrossRefGoogle Scholar
  45. 45.
    Barron D, Jimenez-Lozano E, Irles A, Barbosa J (2000) J Chromatogr 871:381–389CrossRefGoogle Scholar
  46. 46.
    Barron D, Jimenez-Lozano E, Barbosa J (2000) J Chromatogr 919:395–406CrossRefGoogle Scholar
  47. 47.
    Barbosa J, Barron D, Jimenez-Lozano E, Sanz-Nebot V (2001) Anal Chim Acta 437:309–321CrossRefGoogle Scholar
  48. 48.
    Barbosa J, Barron D, Cano J, Jimenez-Lozano E, Sanz-Nebot V, Toro I (2001) J Pharm Biomed Anal 24:1087–1098PubMedCrossRefGoogle Scholar
  49. 49.
    Sanz-Nebot V, Benavente F, Toro I, Barbosa J (2001) J Chromatogr 921:69–79CrossRefGoogle Scholar
  50. 50.
    Wang D, Yang G, Song X (2001) Electrophoresis 22:464–469PubMedCrossRefGoogle Scholar
  51. 51.
    Jimenez-Lozano E, Marques I, Barron D, Beltran JL, Barbosa J (2002) Anal Chim Acta 464:37–45CrossRefGoogle Scholar
  52. 52.
    Sanz-Nebot V, Toro I, Benavente F, Barbosa J (2002) J Chromatogr 942:145–156CrossRefGoogle Scholar
  53. 53.
    Buckenmaier SMC, McCalley DV, Euerby MR (2003) J Chromatogr 1004:71–79CrossRefGoogle Scholar
  54. 54.
    Gong S, Su X, Bo T, Zhang X, Liu H, Li KA (2003) J Sep Sci 26:549–554CrossRefGoogle Scholar
  55. 55.
    Buckenmaier SMC, McCalley DV, Euerby MR (2004) J Chromatogr 1026:251–259CrossRefGoogle Scholar
  56. 56.
    Shalaeva M, Kenseth J, Lombardo F, Bastinz A (2008) J Pharm Sci 97:2581–2606PubMedCrossRefGoogle Scholar
  57. 57.
    Porras SP, Riekkola ML, Kenndler E (2001) Chromatographia 53:290–294CrossRefGoogle Scholar
  58. 58.
    Porras SP, Riekkola M-L, Kenndler E (2001) J Chromatogr 905:259–268CrossRefGoogle Scholar
  59. 59.
    Porras SP, Jyske P, Riekkola M-L, Kenndler E (2001) J Microcolumn Sep 13:149–155Google Scholar
  60. 60.
    Muzikar J, van de Goor T, Gas B, Kenndler E (2002) Anal Chem 74:428–433PubMedCrossRefGoogle Scholar
  61. 61.
    Psurek A, Scriba GKE (2003) Electrophoresis 24:765–773PubMedCrossRefGoogle Scholar
  62. 62.
    Delmar Cantu M, Hillebrand S, Carrilho E (2005) J Chromatogr 1068:99–105CrossRefGoogle Scholar
  63. 63.
    Roses M, Bosch E (2002) J Chromatogr 982:1–30CrossRefGoogle Scholar
  64. 64.
    Yasuda M (1959) Bull Chem Soc Jpn 32:429–432CrossRefGoogle Scholar
  65. 65.
    Cleveland JA, Martin CL, Gluck SJ (1994) J Chromatogr 679:167–171CrossRefGoogle Scholar
  66. 66.
    Perez-Urquiza M, Beltran JL (2001) J Chromatogr 917:331–336CrossRefGoogle Scholar
  67. 67.
    Ishihama Y, Nakamura M, Miwa T, Kajima T, Asakawa N (2002) J Pharm Sci 91:933–942PubMedCrossRefGoogle Scholar
  68. 68.
    Wu X, Gong S, Bo T, Liao Y, Liu H (2004) J Chromatogr 1061:217–223CrossRefGoogle Scholar
  69. 69.
    Mercier J-P, Morin Ph, Dreux M, Tambute A (1998) Chromatographia 48:529–534CrossRefGoogle Scholar
  70. 70.
    Lalwani S, Tutu E, Vigh G (2005) Electrophoresis 26:2503–2510PubMedCrossRefGoogle Scholar
  71. 71.
    Hu Q, Hu G, Zhou T, Fang U (2003) J Pharm Biomed Anal 31:679–684PubMedCrossRefGoogle Scholar
  72. 72.
    Wan H, Holmen AG, Wang Y, Lindberg W, Englund M, Nagard MB, Thompson RA (2003) Rapid Commun Mass Spectrom 17:2639–2648PubMedCrossRefGoogle Scholar
  73. 73.
    Gluck SJ, Steel AJ, Benko MH (1996) J Chromatogr 745:117–125CrossRefGoogle Scholar
  74. 74.
    Kane RS, Glink PT, Chapman RG, McDonald JC, Jensen PK, Gao HY, Pasa-Tolic L, Smith RD, Whitesides GM (2001) Anal Chem 73:4028–4036PubMedCrossRefGoogle Scholar
  75. 75.
    Hagberg J, Duker A, Karlsson S (2002) Chromatographia 56:641–644CrossRefGoogle Scholar
  76. 76.
    Castagnola M, Rossetti DV, Corda M, Pellegrini M, Misiti F, Olianas A, Giardina B, Messana I (1998) Electrophoresis 19:2273–2277PubMedCrossRefGoogle Scholar
  77. 77.
    Geiser L, Henchoz Y, Galland A, Carrupt PA, Veuthey JL (2005) J Sep Sci 28:2374–2380PubMedCrossRefGoogle Scholar
  78. 78.
    Örnskov E, Linusson A, Folestad S (2003) J Pharm Biomed Anal 33:379–391PubMedCrossRefGoogle Scholar
  79. 79.
    Szakacs Z (2006) Electrophoresis 27:3399–3409PubMedCrossRefGoogle Scholar
  80. 80.
    Jankowsky R, Friebe M, Noll B, Johannsen B (1999) J Chromatogr 833:83–96CrossRefGoogle Scholar
  81. 81.
    Jia Z, Ramstad T, Zhong M (2001) Electrophoresis 22:1112–1118PubMedCrossRefGoogle Scholar
  82. 82.
    Kibbey CE, Poole SK, Robinson B, Jackson JD, Durham D (2001) J Pharm Sci 90:1164–1175PubMedCrossRefGoogle Scholar
  83. 83.
    Miller JM, Blackburn AC, Shi Y, Melzak AJ, Ando HY (2002) Electrophoresis 23:2833–2841PubMedCrossRefGoogle Scholar
  84. 84.
    Wan H, Holmen A, Nagard M, Lindberg W (2002) J Chromatogr 979:369–377CrossRefGoogle Scholar
  85. 85.
    Zhou C, Jin Y, Kenseth JR, Stella M, Wehmeyer KR, Heineman WR (2005) J Pharm Sci 94:576–589PubMedCrossRefGoogle Scholar
  86. 86.
    Marsh A, Altria K (2006) Chromatographia 64:327–333CrossRefGoogle Scholar
  87. 87.
    Gong X, Figus M, Plewa J, Levorse DA, Zhou L, Welch CJ (2008) Chromatographia 68:219–225CrossRefGoogle Scholar
  88. 88.
    Caron G, Reymond F, Carrupt PA, Girault HH, Testa B (1999) Pharm Sci Technol Today 2:327–335PubMedCrossRefGoogle Scholar
  89. 89.
    Gocan S, Cimpan G, Comer J (2006) Advances in chromatography. Taylor & Francis, Boca RatonGoogle Scholar
  90. 90.
    Hitzel L, Watt AP, Locker KL (2000) Pharm Res 17:1389–1395PubMedCrossRefGoogle Scholar
  91. 91.
    Wilson DM, Wang X, Walsh E, Rourick RA (2001) Comb Chem High Throughput Screen 4:511–519Google Scholar
  92. 92.
    Gulyaeva N, Zaslavsky A, Lechner P, Chlenov M, McConnell O, Chait A, Kipnis V, Zaslavsky B (2003) Eur J Med Chem 38:391–396PubMedCrossRefGoogle Scholar
  93. 93.
    Gulyaeva N, Zaslavsky A, Lechner P, Chait A, Zaslavsky B (2003) J Peptide Res 61:71–79CrossRefGoogle Scholar
  94. 94.
    Dohta Y, Yamashita T, Horiike S, Nakamura T, Kukami T (2007) Anal Chem 79:8312–8315PubMedCrossRefGoogle Scholar
  95. 95.
    Bouchard G, Carrupt PA, Testa B, Gobry V, Girault HH (2002) Chem Eur J 8:3478–3484PubMedCrossRefGoogle Scholar
  96. 96.
    Nasal A, Siluk D, Kaliszan A (2003) Curr Med Chem 10:381–426PubMedCrossRefGoogle Scholar
  97. 97.
    Kaliszan R, Nasal A, Markuszewski MJ (2003) Anal Bioanal Chem 377:803–811PubMedCrossRefGoogle Scholar
  98. 98.
    Poole SK, Poole CF (2003) J Chromatogr B 797:3–19CrossRefGoogle Scholar
  99. 99.
    Huie CW (2006) Electrophoresis 27:60–75PubMedCrossRefGoogle Scholar
  100. 100.
    Nasal A, Kaliszan R (2006) Curr Comp Aided Drug Des 2:327–340Google Scholar
  101. 101.
    Kaliszan R (2007) Chem Rev 107:3212–3246PubMedCrossRefGoogle Scholar
  102. 102.
    Martel S, Guillarme D, Henchoz Y, Galland A, Veuthey JL, Rudaz S, Carrupt PA (2008) Drug properties: measurement and computation. Wiley-VCH, WeinheimGoogle Scholar
  103. 103.
    Takeda S, Wakida S, Yamane M, Kawahara A, Higashi K (1993) Anal Chem 65:2492CrossRefGoogle Scholar
  104. 104.
    Muijeslaar PGHM, Claessens HA, Cramers CA (1994) Anal Chem 66:635–644CrossRefGoogle Scholar
  105. 105.
    Smith JT, Vinjamoori DV (1995) J Chromatogr B 669:59–66CrossRefGoogle Scholar
  106. 106.
    Herbert BJ, Dorsey JG (1995) Anal Chem 67:744–749CrossRefGoogle Scholar
  107. 107.
    Garcia MA, Diez-Masa JC, Marina ML (1996) J Chromatogr A 742:251–256CrossRefGoogle Scholar
  108. 108.
    Yang S, Bumgarner JG, Kruk LFR, Khaledi MG (1996) J Chromatogr A 721:323–335PubMedCrossRefGoogle Scholar
  109. 109.
    Morin P, Archambault JC, Andre P, Dreux M, Gaydou E (1997) J Chromatogr A 791:289–297CrossRefGoogle Scholar
  110. 110.
    Ferguson PD, Goodall DM, Loran JS (1998) Anal Chem 70:4062CrossRefGoogle Scholar
  111. 111.
    Hanna M, de Biasi V, Bond B, Salter C, Hutt AJ, Camilleri P (1998) Anal Chem 70:2099CrossRefGoogle Scholar
  112. 112.
    Rosés M, Rafols C, Bosch E, Martinez AM, Abraham MH (1999) J Chromatogr A 845:226CrossRefGoogle Scholar
  113. 113.
    Maeder C, Beaudoin GMJ, Hsu EK, Escobar VA, Chambers SM, Kurtin WE, Bushey MM (2000) Electrophoresis 21:706–714PubMedCrossRefGoogle Scholar
  114. 114.
    Garcia-Ruiz C, Garcia MA, Marina ML (2000) Electrophoresis 21:2424–2431PubMedCrossRefGoogle Scholar
  115. 115.
    Mrestani Y, Janich M, Ruttinger HH, Neubert RH (2000) J Chromatogr A 873:237–246PubMedCrossRefGoogle Scholar
  116. 116.
    Trone MD, Leonard MS, Khaledi MG (2000) Anal Chem 72:1228–1235PubMedCrossRefGoogle Scholar
  117. 117.
    Mrestani Y, Marestani Z, Neubert RH (2001) Electrophoresis 22:3573–3577PubMedCrossRefGoogle Scholar
  118. 118.
    Mrestani Y, Marestani Z, Neubert RH (2001) J Pharm Biomed Anal 26:883–889PubMedCrossRefGoogle Scholar
  119. 119.
    Taillardat-Bertschinger A, Carrupt PA, Testa B (2002) Eur J Pharm Sci 15:225–234PubMedCrossRefGoogle Scholar
  120. 120.
    Detroyer A, Vander HY, Cambre I, Massart DL (2003) J Chromatogr A 986:227–238PubMedCrossRefGoogle Scholar
  121. 121.
    Annoura H, Nakanishi K, Uesugi M, Fukunaga A, Miyajima A, Tamura-Horikawa Y, Tamura S (1999) Bioorg Med Chem Lett 9:2999–3002PubMedCrossRefGoogle Scholar
  122. 122.
    Müller L, Bednar P, Bartak P, Lemr K, Sevcik J (2005) J Sep Sci 28:1285–1290PubMedCrossRefGoogle Scholar
  123. 123.
    Razak JL, Cutak BJ, Larive CK, Lunte CE (2001) Pharm Res 18:104–111PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Burns ST, Khaledi MG (2002) J Pharm Sci 91:1601–1612PubMedCrossRefGoogle Scholar
  125. 125.
    Klotz WL, Schure MR, Foley JP (2002) J Chromatogr A 962:207–219PubMedCrossRefGoogle Scholar
  126. 126.
    Agbodjan AA, Bui H, Khaledi MG (2001) Langmuir 17:2893–2899CrossRefGoogle Scholar
  127. 127.
    Örnskov E, Gottfries J, Erickson M, Folestad S (2005) J Pharm Pharmacol 57:435–442PubMedCrossRefGoogle Scholar
  128. 128.
    Ishihama Y, Oda Y, Uchikawa K, Asakawa N (1995) Anal Chem 67:1588–1595CrossRefGoogle Scholar
  129. 129.
    Ishihama Y, Oda Y, Asakawa N (1996) Anal Chem 68:1032Google Scholar
  130. 130.
    Ishihama Y, Oda Y, Asakawa N (1996) Anal Chem 68:4284Google Scholar
  131. 131.
    Gluck SJ, Benkö MH, Hallberg RK, Steele KP (1996) J Chromatogr A 744:141–146CrossRefGoogle Scholar
  132. 132.
    Poole SK, Durham D, Kibbey C (2000) J Chromatogr B 745:117–126Google Scholar
  133. 133.
    Caliaro GA, Herbots CA (2001) J Pharm Biomed Anal 26:427–434PubMedCrossRefGoogle Scholar
  134. 134.
    Klotz WL, Schure MR, Foley JP (2001) J Chromatogr A 930:145–154PubMedCrossRefGoogle Scholar
  135. 135.
    Wasserman MA, Sundell CL, Kunsch C, Edwards D, Meng CQ, Medford RM (2003) Am J Cardiol 91:34A–40AGoogle Scholar
  136. 136.
    Lucangioli SE, Kenndler E, Carlucci A, Tripodi VP, Scioscia SL, Carducci CN (2003) J Pharm Biomed Anal 33:871–878PubMedCrossRefGoogle Scholar
  137. 137.
    Lucangioli SE, Carducci CN, Scioscia SL, Carlucci A, Bregni C, Kenndler E (2003) Electrophoresis 24:984–991PubMedCrossRefGoogle Scholar
  138. 138.
    Ostergaard J, Hansen SH, Larsen C, Schou C, Heegaard NH (2003) Electrophoresis 24:1038–1046PubMedCrossRefGoogle Scholar
  139. 139.
    Poole SK, Patel S, Dehring K, Workman H, Dong J (2003) J Chromatogr B 793:265–274Google Scholar
  140. 140.
    Wehmeyer KR, Tu J, Jin Y, King S, Stella M, Stanton DT, Kenseth J, Wong KS (2003) LC–GC N Am 21:1078–1088Google Scholar
  141. 141.
    Gong S, Bo T, Huang L, Li KA, Liu H (2004) Electrophoresis 25:1058–1064PubMedCrossRefGoogle Scholar
  142. 142.
    Wong KS, Kenseth J, Strasburg R (2004) J Pharm Sci 93:916–931PubMedCrossRefGoogle Scholar
  143. 143.
    Rappel C, Galanski M, Yasemi A, Habala L, Keppler BK (2005) Electrophoresis 26:878–884PubMedCrossRefGoogle Scholar
  144. 144.
    Tu J, Halsall HB, Seliskar CJ, Limbach PA, Arias F, Wehmeyer KR, Heineman WR (2005) J Pharm Biomed Anal 38:1–7PubMedCrossRefGoogle Scholar
  145. 145.
    Xia Z, Jiang X, Mu X, Chen H (2008) Electrophoresis 29:835–842PubMedCrossRefGoogle Scholar
  146. 146.
    Abraham MH, Treiner C, Roses M, Rafols C, Ishihama Y (1996) J Chromatogr A 752:243–249CrossRefGoogle Scholar
  147. 147.
    Mrestani Y, Neubert RHH, Krause A (1998) Pharm Res 15:799–801PubMedCrossRefGoogle Scholar
  148. 148.
    Hanse SH (2003) Electrophoresis 24:3900–3907CrossRefGoogle Scholar
  149. 149.
    Marsh A, Clark B, Broderick M, Power J, Donegan S, Altria K (2004) Electrophoresis 25:3970–3980PubMedCrossRefGoogle Scholar
  150. 150.
    Altria K, Marsh A, Sanger-van de Griend C (2006) Electrophoresis 27:2263–2282PubMedCrossRefGoogle Scholar
  151. 151.
    McEvoy E, Marsh A, Altria K, Donegan S, Power J (2007) Electrophoresis 28:193–207PubMedCrossRefGoogle Scholar
  152. 152.
    Schappler J, Guillarme D, Prat J, Veuthey JL, Rudaz S (2007) Electrophoresis 28:3078–3087PubMedCrossRefGoogle Scholar
  153. 153.
    Hommerson P, Khan AM, de Jong GJ, Somsen GW (2008) J Chromatogr A 1204:197–203PubMedCrossRefGoogle Scholar
  154. 154.
    Schappler J, Guillarme D, Rudaz S, Veuthey JL (2008) Electrophoresis 29:11–19PubMedCrossRefGoogle Scholar
  155. 155.
    Valko K (2004) J Chromatogr A 1037:299–310PubMedCrossRefGoogle Scholar
  156. 156.
    Barbato F (2006) Curr Comp Aided Drug Des 2:341–352Google Scholar
  157. 157.
    Giaginis C, Tsantili-Kakoulidou A (2008) J Liq Chromatogr R T 31:79–96Google Scholar
  158. 158.
    Giaginis C, Tsantili-Kakoulidou A (2008) J Pharm Sci 97:2984–3004PubMedCrossRefGoogle Scholar
  159. 159.
    Martel S, Gasparik V, Carrupt PA (2008) Hit and lead profiling. Wiley-VCH, WeinheimGoogle Scholar
  160. 160.
    Baczek T, Markuszewski M, Kaliszan R (2000) J High Res Chromatogr 23:667–676Google Scholar
  161. 161.
    Balogh GT, Szanto Z, Forrai E, Gyorffy W, Lopata A (2005) J Pharm Biomed Anal 39:1057–1062PubMedCrossRefGoogle Scholar
  162. 162.
    Grover M, Gulati M, Singh B, Singh S (2005) QSAR Comb Sci 24:639–648CrossRefGoogle Scholar
  163. 163.
    Valko K, Slegel P (1993) J Chromatogr 631:49–61CrossRefGoogle Scholar
  164. 164.
    Vrakas D, Panderi I, Hadjipavlou-Litina D, Tsantili-Kakoulidou A (2005) QSAR Comb Sci 24:254–260CrossRefGoogle Scholar
  165. 165.
    Pagliara A, Khamis E, Trinh A, Carrupt PA, Tsai RS, Testa B (1995) J Liq Chromatogr 18:1721–1745Google Scholar
  166. 166.
    Du CM, Valko K, Bevan C, Reynolds D, Abraham MH (1998) Anal Chem 70:4228–4234CrossRefGoogle Scholar
  167. 167.
    Du CM, Valko K, Bevan C, Reynolds D, Abraham MH (2001) J Liq Chromatogr R T 24:635–649Google Scholar
  168. 168.
    Zhao Y, Jona J, Chow DT, Rong H, Semin D, Xia X, Zanon R, Spancake C, Maliski E (2002) Rapid Commun Mass Spectrom 16:1548–1555PubMedCrossRefGoogle Scholar
  169. 169.
    Hallgas B, Patonay T, Kiss-Szikszai A, Dobos Z, Hollosy F, Eros D, Orfi L, Keri G, Idei M (2004) J Chromatogr B 801:229–235CrossRefGoogle Scholar
  170. 170.
    Hallgas B, Dobos Z, Osz E, Hollosy F, Schwab RE, Szabo EZ, Eros D, Idei M, Keri G, Lorand T (2005) J Chromatogr B 819:283–291CrossRefGoogle Scholar
  171. 171.
    Stella C, Galland A, Liu X, Testa B, Rudaz S, Veuthey JL, Carrupt PA (2005) J Sep Sci 28:2350–2362PubMedCrossRefGoogle Scholar
  172. 172.
    Hallgas B, Dobos Z, Agocs A, Idei M, Keri G, Lorand T, Meszaros G (2007) J Chromatogr B 856:148–155CrossRefGoogle Scholar
  173. 173.
    Musilek K, Jampilek J, Dohnal J, Jun D, Gunn-Moore F, Dolezal M, Kuca K (2008) Anal Bioanal Chem 391:367–372PubMedCrossRefGoogle Scholar
  174. 174.
    Snyder LR, Dolan JW, Gant JR (1979) J Chromatogr A 165:3–30CrossRefGoogle Scholar
  175. 175.
    Kaliszan R, Haber P, Baczek T, Siluk D (2001) Pure Appl Chem 73:1465–1475CrossRefGoogle Scholar
  176. 176.
    Kaliszan R, Wiczling P, Markuszewski MJ (2004) Anal Chem 76:749–760PubMedCrossRefGoogle Scholar
  177. 177.
    Dias NC, Nawas MI, Poole CF (2003) Analyst 128:427–433PubMedCrossRefGoogle Scholar
  178. 178.
    Krass JD, Jastorff B, Genieser H-G (1997) Anal Chem 69:2575–2581PubMedCrossRefGoogle Scholar
  179. 179.
    Donovan SF, Pescatore MC (2002) J Chromatogr A 952:47–61PubMedCrossRefGoogle Scholar
  180. 180.
    Gulyaeva N, Zaslavsky A, Lechner P, Chlenov M, Chait A, Zaslavsky B (2002) Eur J Pharm Sci 17:81–93PubMedCrossRefGoogle Scholar
  181. 181.
    Kerns EH, Di L, Petusky S, Kleintop T, Huryn D, McConnell O, Carter G (2003) J Chromatogr B 791:381–388CrossRefGoogle Scholar
  182. 182.
    Welerowicz T, Buszewski B (2005) Biomed Chromatogr 19:725–736PubMedCrossRefGoogle Scholar
  183. 183.
    Valko K, Bevan C, Reynolds D (1997) Anal Chem 69:2022–2029PubMedCrossRefGoogle Scholar
  184. 184.
    Valko K, Du CM, Bevan C, Reynolds DP, Abraham MH (2001) Curr Med Chem 8:1137–1146PubMedCrossRefGoogle Scholar
  185. 185.
    Camurri G, Zaramella A (2001) Anal Chem 73:3716–3722PubMedCrossRefGoogle Scholar
  186. 186.
    Zissimos AM, Abraham MH, Barker MC, Box KJ, Tam KY (2002) J Chem Soc 3:470–477Google Scholar
  187. 187.
    Bartalis J, Halaweish FT (2005) J Chromatogr B 818:159–166CrossRefGoogle Scholar
  188. 188.
    Fuguet E, Rafols C, Bosch E, Roses M (2007) J Chromatogr A 1173:110–119PubMedCrossRefGoogle Scholar
  189. 189.
    Kaliszan R, Haber P, Baczek T, Siluk D, Valko K (2002) J Chromatogr A 965:117–227PubMedCrossRefGoogle Scholar
  190. 190.
    Henchoz Y, Guillarme D, Martel S, Rudaz S, Veuthey JL, Carrupt PA (2009) Anal Chem (submitted)Google Scholar
  191. 191.
    Snyder LR, Kirkland JJ (1979) Introduction to modern liquid chromatography. Wiley, ChichesterGoogle Scholar
  192. 192.
    Minick DJ, Frenz JH, Patrick MA, Brent DA (1988) J Med Chem 31:1923–1933PubMedCrossRefGoogle Scholar
  193. 193.
    Lombardo F, Shalaeva MY, Tupper KA, Gao F, Abraham MH (2000) J Med Chem 43:2922–2928PubMedCrossRefGoogle Scholar
  194. 194.
    Lombardo F, Shalaeva MY, Tupper KA, Gao F (2001) J Med Chem 44:2490–2497PubMedCrossRefGoogle Scholar
  195. 195.
    Ayouni L, Cazorla G, Chaillou D, Herbreteau B, Rudaz S, Lanteri P, Carrupt PA (2005) Chromatographia 62:251–255CrossRefGoogle Scholar
  196. 196.
    Liu X, Tanaka H, Yamauchi A, Testa B, Chuman H (2005) J Chromatogr A 1091:51–59PubMedCrossRefGoogle Scholar
  197. 197.
    Giaginis C, Theocharis S, Tsantili-Kakoulidou A (2006) Anal Chim Acta 573:311–318PubMedCrossRefGoogle Scholar
  198. 198.
    Dellis D, Giaginis C, Tsantili-Kakoulidou A (2007) J Pharm Biomed Anal 44:57–62PubMedCrossRefGoogle Scholar
  199. 199.
    Giaginis C, Theocharis S, Tsantili-Kakoulidou A (2007) J Chromatogr A 1166:116–125PubMedCrossRefGoogle Scholar
  200. 200.
    Giaginis C, Theocharis S, Tsantili-Kakoulidou A (2007) J Chromatogr B 857:181–187CrossRefGoogle Scholar
  201. 201.
    Benhaim D, Grushka E (2008) J Chromatogr A 1209:111–119PubMedCrossRefGoogle Scholar
  202. 202.
    Tate PA, Dorsey JG (2004) J Chromatogr A 1042:37–48PubMedCrossRefGoogle Scholar
  203. 203.
    Escuder-Gilabert L, Martinez-Pla JJ, Sagrado S, Villanueva-Camanas RM, Medina-Hernandez MJ (2003) J Chromatogr B 797:21–35CrossRefGoogle Scholar
  204. 204.
    Barbato F, di Martino G, Grumetto L, La Rotonda MI (2005) Eur J Pharm Sci 25:379–386PubMedCrossRefGoogle Scholar
  205. 205.
    Vrakas D, Giaginis C, Tsantili-Kakoulidou A (2006) J Chromatogr A 1116:158–164PubMedCrossRefGoogle Scholar
  206. 206.
    Barbato F, Cirocco V, Grumetto L, La Rotonda MI (2007) Eur J Pharm Sci 31:288–297PubMedCrossRefGoogle Scholar
  207. 207.
    Vrakas D, Giaginis C, Tsantili-Kakoulidou A (2008) J Chromatogr A 1187:67–78PubMedCrossRefGoogle Scholar
  208. 208.
    Taillardat-Bertschinger A, Galland A, Carrupt PA, Testa B (2002) J Chromatogr A 953:39–53CrossRefGoogle Scholar
  209. 209.
    Hemström P, Irgum K (2006) J Sep Sci 29:1784–1821PubMedCrossRefGoogle Scholar
  210. 210.
    Jandera P (2008) J Sep Sci 31:1421–1437PubMedCrossRefGoogle Scholar
  211. 211.
    Ikegami T, Tomomatsu K, Takubo H, Horie K, Tanaka N (2008) J Chromatogr A 1184:474–503PubMedCrossRefGoogle Scholar
  212. 212.
    Dejaegher B, Mangelings D, Heyden YV (2008) J Sep Sci 31:1438–1448PubMedCrossRefGoogle Scholar
  213. 213.
    Bard B, Carrupt PA, Martel S (2009) J Med Chem (submitted)Google Scholar
  214. 214.
    Bard B, Martel S, Carrupt PA (2009) J Chromatogr A (submitted)Google Scholar
  215. 215.
    Kerns EH, Di L (2006) Curr Drug Metab 7:457–466PubMedCrossRefGoogle Scholar
  216. 216.
    Braddy AC, Janaky T, Prokai L (2002) J Chromatogr A 966:81–87PubMedCrossRefGoogle Scholar
  217. 217.
    Kangas H, Kotiaho T, Salminen T, Kostiainen R (2001) Rapid Commun Mass Spectrom 15:1501–1505PubMedCrossRefGoogle Scholar
  218. 218.
    Liu H, Carter GT, Tischler M (2001) Rapid Commun Mass Spectrom 15:1533–1538PubMedCrossRefGoogle Scholar
  219. 219.
    Mazzeo JR, Neue UD, Kele M, Plumb RS (2005) Anal Chem 77:460–467Google Scholar
  220. 220.
    Nguyen DTT, Guillarme D, Rudaz S, Veuthey JL (2006) J Sep Sci 29:1836–1848PubMedCrossRefGoogle Scholar
  221. 221.
    Guillarme D, Nguyen DTT, Rudaz S, Veuthey JL (2007) J Chromatogr A 1149:20–29PubMedCrossRefGoogle Scholar
  222. 222.
    Henchoz Y, Guillarme D, Rudaz S, Veuthey JL, Carrupt PA (2008) J Med Chem 51:396–399PubMedCrossRefGoogle Scholar
  223. 223.
    Kaliszan R, Wiczling P, Markuszewski MJ (2004) J Chromatogr A 1060:165–175PubMedCrossRefGoogle Scholar
  224. 224.
    Wiczling P, Markuszewski MJ, Kaliszan R (2004) Anal Chem 76:3069–3077PubMedCrossRefGoogle Scholar
  225. 225.
    Kaliszan R, Wiczling P (2005) Anal Bioanal Chem 382:718–727PubMedCrossRefGoogle Scholar
  226. 226.
    Wiczling P, Markuszewski MJ, Kaliszan M, Kaliszan R (2005) Anal Chem 77:449–458PubMedCrossRefGoogle Scholar
  227. 227.
    Wiczling P, Kawczak P, Nasal A, Kaliszan R (2006) Anal Chem 78:239–249PubMedCrossRefGoogle Scholar
  228. 228.
    Amidon GL, Lennernas H, Shah VP, Crison JR (1995) Pharm Res 12:413–420PubMedCrossRefGoogle Scholar
  229. 229.
    van de Waterbeemd H (1998) Eur J Pharm Sci 7:1–3PubMedCrossRefGoogle Scholar
  230. 230.
    Di L, Kerns EH (2006) Drug Discov Today 11:446–451PubMedCrossRefGoogle Scholar
  231. 231.
    Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Adv Drug Deliv Rev 23:3–25CrossRefGoogle Scholar
  232. 232.
    Grant DJW, Higuchi T (1990) Solubility behaviour of organic compounds. Wiley, New YorkGoogle Scholar
  233. 233.
    Avdeef A (1998) Pharm Pharmacol Commun 4:165–178Google Scholar
  234. 234.
    Avdeef A, Berger CM, Brownell C (2000) Pharm Res 17:85–89PubMedCrossRefGoogle Scholar
  235. 235.
    Avdeef A, Berger CM (2001) Eur J Pharm Sci 14:281–291PubMedCrossRefGoogle Scholar
  236. 236.
    Glomme A, März J, Dressman JB (2005) J Pharm Sci 94:1–16PubMedCrossRefGoogle Scholar
  237. 237.
    Stuart M, Box K (2005) Anal Chem 77:983–990PubMedCrossRefGoogle Scholar
  238. 238.
    Box KJ, Völgyi G, Baka E, Stuart M, Takacs-Novak K, Comer JEA (2006) J Pharm Sci 95:1298–1307PubMedCrossRefGoogle Scholar
  239. 239.
    Martel S, Castella ME, Bajot F, Ottaviani G, Bard B, Henchoz Y, Gross Valloton B, Reist M, Carrupt PA (2005) Chimia 59:308–314CrossRefGoogle Scholar
  240. 240.
    Bevan CD (2000) Anal Chem 72:1781–1787PubMedCrossRefGoogle Scholar
  241. 241.
    Pan L, Ho Q, Tsutsui K, Takahashi L (2001) J Pharm Sci 90:521–529PubMedCrossRefGoogle Scholar
  242. 242.
    Dehring KA, Workman HL, Miller KD, Mandagere A, Poole SK (2004) J Pharm Biomed Anal 36:447–456PubMedCrossRefGoogle Scholar
  243. 243.
    Fligge TA, Schuler A (2006) J Pharm Biomed Anal 42:449–454Google Scholar
  244. 244.
    Chen TM, Shen H, Zhu C (2002) Comb Chem High Throughput Screen 5:575–581PubMedCrossRefGoogle Scholar
  245. 245.
    Millipore Corp. (2003) Multiscreen solubility filter plate. Millipore Corporation, BillericaGoogle Scholar
  246. 246.
    Yamashita T, Dohta Y, Nakamura T, Fukami T (2008) J Chromatogr A 1182:72–76PubMedCrossRefGoogle Scholar
  247. 247.
    Bard B, Martel S, Carrupt PA (2008) Eur J Pharm Sci 33:230–240PubMedCrossRefGoogle Scholar
  248. 248.
    Loftsson T, Hreinsdottir D (2006) AAPS PharmSciTech 7:E1–E4CrossRefGoogle Scholar
  249. 249.
    Wei H, Löbenberg R (2006) Eur J Pharm Sci 29:45–52PubMedCrossRefGoogle Scholar
  250. 250.
    Seadeek C, Ando H, Bhattachar SN, Heimbach T, Sonnenberg JL, Blackburn AC (2007) J Pharm Biomed Anal 43:1660–1666PubMedCrossRefGoogle Scholar
  251. 251.
    Hewitt M, Madden JC, Rowe PH, Cronin MTD (2007) SAR QSAR Environ Res 18:57–76PubMedCrossRefGoogle Scholar
  252. 252.
    Roy D, Ducher F, Laumain A, Legendre JY (2001) Drug Dev Ind Pharm 27:107–109PubMedCrossRefGoogle Scholar
  253. 253.
    Tan H, Semin D, Wacker M, Cheetham J (2005) JALA 10:364–373Google Scholar
  254. 254.
    Sugano K, Kato T, Suzuki K, Keiko K, Sujaku T, Mano T (2006) J Pharm Sci 95:2115–2122PubMedCrossRefGoogle Scholar
  255. 255.
    Hancock BC, Parks M (2000) Pharm Res 17:397–404PubMedCrossRefGoogle Scholar
  256. 256.
    Pudipeddi M, Serajuddin ATM (2005) J Pharm Sci 94:929–939PubMedCrossRefGoogle Scholar
  257. 257.
    Chen XQ, Venkatesh S (2004) Pharm Res 21:1758–1761PubMedCrossRefGoogle Scholar
  258. 258.
    Jeanie Cherng JP, Gonzalez-Zugasti J, Kane NR, Cima M, Lemmo AV (2004) JALA 9:228–237Google Scholar
  259. 259.
    Mithani SD, Bakatselou V, TenHoor CN, Dressman JB (1996) Pharm Res 13:163–167PubMedCrossRefGoogle Scholar
  260. 260.
    Glomme A, März J, Dressman JB (2006) Pharmacokinetic profiling in drug research. Verlag Helvetica Chimica Acta, ZurichGoogle Scholar
  261. 261.
    Bakatselou V, Oppenheim RC, Dressman JB (1991) Pharm Res 8:1461–1469PubMedCrossRefGoogle Scholar
  262. 262.
    Dressman JB, Berardi RR, Dermentzoglou LC, Russell TL, Schmaltz SP, Barnett JL, Jarvenpaa KM (1990) Pharm Res 7:756–761PubMedCrossRefGoogle Scholar
  263. 263.
    Galia E, Nicolaides E, Hörter D, Löbenberg R, Reppas C, Dressman JB (1998) Pharm Res 15:698–705PubMedCrossRefGoogle Scholar
  264. 264.
    Jantratid E, Janssen N, Reppas C, Dressman JB (2008) Pharm Res 25:1663–1676PubMedCrossRefGoogle Scholar
  265. 265.
    Haines TH (1983) Proc Natl Acad Sci USA 80:160–164PubMedCrossRefGoogle Scholar
  266. 266.
    Plemper van Balen G, Marca-Martinet C, Caron G, Bouchard G, Reist M, Carrupt PA, Fruttero R, Gasco A, Testa B (2004) Med Res Rev 24:399–324CrossRefGoogle Scholar
  267. 267.
    Miteva MA, Lee WH, Montes MO, Villoutreix BO (2005) J Med Chem 48:6012–6022PubMedCrossRefGoogle Scholar
  268. 268.
    Ottiger C, Wunderli-Allenspach H (1997) Eur J Pharm Sci 5:223–231CrossRefGoogle Scholar
  269. 269.
    Pauletti GM, Wunderli-Allenspach H (1994) Eur J Pharm Sci 1:273–282CrossRefGoogle Scholar
  270. 270.
    Krämer SD, Wunderli-Allenspach H (1996) Pharm Res 13:1851–1855PubMedCrossRefGoogle Scholar
  271. 271.
    Krämer SD, Braun A, Jakits-Deiser C, Wunderli-Allenspach H (1998) Pharm Res 15:739–744PubMedCrossRefGoogle Scholar
  272. 272.
    Qi LW, Li P, Li SL, Sheng LH, Li RY, Song Y, Li HJ (2006) J Sep Sci 29:2211–2220PubMedCrossRefGoogle Scholar
  273. 273.
    Seydel JK (1991) TIPS 12:368–371PubMedGoogle Scholar
  274. 274.
    Xian DL, Huang KL, Liu SQ, Xiao JY (2008) Chin J Chem 26:671–676CrossRefGoogle Scholar
  275. 275.
    Wang Y, Sun J, Liu H, He Z (2007) Electrophoresis 28:2391–2395PubMedCrossRefGoogle Scholar
  276. 276.
    Wang Y, Sun J, Liu H, Wang Y, He Z (2007) Chromatographia 65:173–177CrossRefGoogle Scholar
  277. 277.
    Krämer SD (2001) Pharmacokinetic optimization in drug research: biological, physicochemical and computational strategies. Wiley-VHCA, ZurichGoogle Scholar
  278. 278.
    Escher BI, Schwarzenbach RP, Westall JC (2000) Environ Sci Technol 34:3954–3961CrossRefGoogle Scholar
  279. 279.
    Loidl-Stahlhofen A, Eckert A, Hartmann T, Schöttner M (2001) J Pharm Sci 90:599–606PubMedCrossRefGoogle Scholar
  280. 280.
    Loidl-Stahlhofen A, Hartmann T, Schottner M, Rohring C, Brodowsky H, Schmitt J, Keldenich J (2001) Pharm Res 18:1782–1788PubMedCrossRefGoogle Scholar
  281. 281.
    Escher BI, Schwarzenbach RP, Westall JC (2000) Environ Sci Technol 34:3962–3968CrossRefGoogle Scholar
  282. 282.
    Hartmann T, Schmitt J, Röhring C, Nimptsch D, Nöller J, Mohr C (2006) Curr Drug Del 3:181–192CrossRefGoogle Scholar
  283. 283.
    Kansy M, Senner F, Gubernator K (1998) J Med Chem 41:1007–1010PubMedCrossRefGoogle Scholar
  284. 284.
    Sugano K, Hamada H, Machida M, Ushio H, Saitoh K, Terada K (2001) Int J Pharm 228:181–188PubMedCrossRefGoogle Scholar
  285. 285.
    Wohnsland F, Faller B (2001) J Med Chem 44:923–930PubMedCrossRefGoogle Scholar
  286. 286.
    Di L, Kerns EH, Fan K, McConnell OJ, Carter GT (2003) Eur J Med Chem 38:223–232PubMedCrossRefGoogle Scholar
  287. 287.
    Carrara S, Reali V, Misiano P, Dondio G, Bigogno C (2007) Int J Pharm 345:125–133PubMedCrossRefGoogle Scholar
  288. 288.
    Ottaviani G, Martel S, Carrupt PA (2006) J Med Chem 49:3948–3954PubMedCrossRefGoogle Scholar
  289. 289.
    Liu H, Sabus C, Carter GT, Du C, Avdeef A, Titeler M (2003) Pharm Res 20:1820–1826PubMedCrossRefGoogle Scholar
  290. 290.
    Mensch J, Noppe M, Adriaensen J, Melis A, Mackie C, Augustijns P, Brewster ME (2007) J Chromatogr B 847:182–187CrossRefGoogle Scholar
  291. 291.
    Hakala KS, Laitinen L, Kaukonen AM, Hirvonen J, Kostiainen R, Kotiaho T (2003) Anal Chem 75:5969–5977PubMedCrossRefGoogle Scholar
  292. 292.
    Caldwell GW, Masucci JA, Evangelisto M, White R (1998) J Chromatogr A 800:161–169PubMedCrossRefGoogle Scholar
  293. 293.
    Stewart BH, Chan OH (1998) J Pharm Sci 87:1471–1478PubMedCrossRefGoogle Scholar
  294. 294.
    Taillardat-Bertschinger A, Barbato F, Quercia MT, Carrupt PA, Reist M, La Rotonda MI, Testa B (2002) Helv Chim Acta 85:519–532CrossRefGoogle Scholar
  295. 295.
    Avdeef A, Box KJ, Comer JEA, Hibbert C, Tam KY (1998) Pharm Res 15:209–215PubMedCrossRefGoogle Scholar
  296. 296.
    Taillardat-Bertschinger A, Carrupt PA, Barbato F, Testa B (2003) J Med Chem 46:655–665PubMedCrossRefGoogle Scholar
  297. 297.
    Yoon CH, Shin BS, Chang HS, Kwon LS, Kim HY, Yoo SE, Yoo SD (2004) Chromatographia 60:399–404CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Yveline Henchoz
    • 1
  • Bruno Bard
    • 1
  • Davy Guillarme
    • 1
  • Pierre-Alain Carrupt
    • 1
  • Jean-Luc Veuthey
    • 1
  • Sophie Martel
    • 1
    Email author
  1. 1.School of Pharmaceutical SciencesUniversity of Geneva, University of LausanneGeneva 4Switzerland

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