803
Views
92
CrossRef citations to date
0
Altmetric
Original Articles

Current State of the Art in HPLC Methodology for Lipophilicity Assessment of Basic Drugs. A Review

&
Pages 79-96 | Received 28 Feb 2007, Accepted 28 Apr 2007, Published online: 06 Nov 2007

References

  • Lipinski , C. A. , Lombardo , F. , Dominy , B. W. and Feeney , P. J. 1997 . Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings . Adv. Drug. Deliv. Rev. , 23 : 3 – 25 .
  • Testa , B. , Crivori , P. , Reist , M. and Carrupt , P. A. 2000 . The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples . Perspect. Drug Discov. , 17 : 179 – 211 .
  • Hansch , C. 1981 . The physicochemical approach to drug design and discovery (QSAR) . Drug Dev. Res. , 1 : 267 – 309 .
  • Smith , D. A. , Jones , B. and Walker , D. K. 1996 . Design of drugs involving the concepts and theories on drug metabolism and pharmakokinetics . Med. Res. Rev. , 16 : 243 – 266 .
  • Mannhold , A. and van Waterbeemd , H. 2001 . Substructure and whole molecule approaches for calculating log P . J. Comp.‐Aid. Mol. Des. , 15 : 337 – 354 .
  • Vrakas , D. , Tsantili‐Kakoulidou , A. and Hadjipavlou‐Litina , D. 2003 . Exploring the consistency of logP estimation for substituted coumarins . Quant. Struct.‐Act. Relat. , 22 : 622 – 629 .
  • Dearden , J. C. and Bresnen , G. M. 1988 . The measurement of partition coefficients . Quant. Struct.‐Act. Relat. , 7 : 133 – 144 .
  • Hersey , A. , Hill , A. P. , Hyde , R. M. and Livingstone , D. J. 1989 . Principles of method selection in partition studies . Quant. Struct.‐Act. Relat. , 8 : 288 – 296 .
  • Avdeef , A. 1993 . Refinement of partition coefficients and ionization constants of multiprotic substances . J. Pharm. Sci. , 82 : 183 – 190 . pH‐Metric logP. 2.
  • Avdeef , A. and Box , K. J. 1995 . Sirius Technical Application Notes (STAN) Vol. 2 , Forest Row, UK : Sirius Analytical Instruments Ltd. .
  • Braumann , T. 1986 . Determination of hydrophobic parameters by reversed‐phase liquid chromatography: theory, experimental techniques, and application in studies on quantitative structure‐activity relationships . J. Chromatogr. , 373 : 191 – 225 .
  • Dorsey , J. G. and Khaledi , M. G. 1993 . Hydrophobicity estimations by reversed‐phase liquid chromatography. Implications for biological partitioning processes . J. Chromatogr. A , 656 : 485 – 499 .
  • Van de Waterbeemd , H. , Kansy , M. , Wagner , B. and Fischer , H. 1996 . “ Lipophilicity measurement by high performance liquid chromatography (RP‐HPLC) ” . In Lipophilicity in Drug Action and Toxicology Edited by: Pilska , V. , Testa , B. and van de Waterbeemd , H. 73 Weinheim : VCH .
  • Kaliszan , R. 1990 . High‐performance liquid‐chromatographic methods and procedures of hydrophobicity determination . Quant. Struct.‐Act. Relat. , 9 : 83 – 87 .
  • Bechalany , A. , Tsantili‐Kakoulidou , A. , El Tayar , N. and Testa , B. 1991 . Measurement of lipophilicity indices by reversed‐phase high‐performance liquid chromatography: comparison of two stationary phases and various eluents . J. Chromatogr. , 541 : 221 – 229 .
  • Slater , B. , McCormack , A. , Avdeef , A. and Comer , J. E.A. 1994 . pH Metric logP. 4. Comparison of partition coefficients determined by shake‐flask, HPLC and potentiometric methods . J. Pharm. Sci. , 83 : 1280 – 1283 .
  • Kramer , S. 2001 . “ Liposomes/water partitioning: Theory techniques applications ” . In Pharmacokinetic Optimization in Drug Research Edited by: Testa , B. , van de Waterbeemd , H. , Folkers , G. and Guy , R. Weinheim : Verlag Helvetica Chimica Acta: Zürich and Wiley-VCH .
  • Pidgeon , C. , Ong , S. , Liu , H. , Qui , X. , Pidgeon , M. , Dantzig , A. H. , Munroe , J. , Hornback , W. J. , Kasher , J. S. , Glunz , L. and Szczerba , T. 1995 . IAM chromatography: An in vitro screen for predicting drug membrane permeability . J. Med. Chem. , 38 : 590 – 594 .
  • Ong , S. , Liu , H. and Pidgeon , C. 1996 . Immobilized artificial membrane chromatography: measurements of membrane partition coefficient and predicting drug membrane permeability . J. Chromatogr. A , 728 : 113 – 128 .
  • Yamagami , C. , Yokota , M. , Takao , N. and Alan , R. 1994 . Hydrophobicity parameters determined by reversed‐phase liquid chromatography. IX: Relationship between capacity factor and water‐octanol partition coefficient of monosubstituted pyrimidines . Chem. Pharm. Bull. , 42 : 907 – 912 .
  • Tsantili‐Kakoulidou , A. and Antoniadou‐Vyza , A. 1989 . “ Determination of the partition coefficients of adamantyl derivatives by reversed phase TLC and HPLC ” . In QSAR: Quantitative Structure‐Activity Relationships in Drug Design 71 – 74 . Liss, Inc. . Alan R.
  • Abraham , M. A. , Chadha , H. S. and Leo , A. J. 1994 . Hydrogen bonding XXXV. Relationship between HPLC capacity factors and water‐octanol partition coefficients . J. Chromatogr. A , 685 : 203 – 211 .
  • Abraham , M. A. , Chadha , H. S. , Leitao , R. A.E. , Mitchell , R. C. , Lambert , W. J. , Kaliszan , R. , Nasal , A. and Haber , P. 1997 . Determination of solute lipophilicity, as logP(octanol) and logP(alkane) using poly(styrene‐divinylbenzene) and immobilized artificial membrane stationary phases in reversed‐phase high‐performance liquid chromatography . J. Chromatogr. A , 685 : 203 – 211 . 766, 35–47
  • Vrakas , D. , Panderi , I. , Hadjipavlou‐Litina , D. and Tsantili‐Kakoulidou , A. 2005 . Investigation of the relationships between logP and various chromatographic indices for a series of substituted coumarins. Evaluation of their similarity/dissimilarity using multivariate statistics . Quant. Struct.‐Act. Relat. , 24 : 254 – 269 .
  • Kaliszan , R. 1990 . High performance liquid chromatographic methods and procedures of hydrophobicity determination . Quant. Struct.‐Act. Relat. , 9 : 83 – 87 .
  • Lombardo , F. , Shalaeva , M. Y. , Tupper , K. A. and Gao , F. 2001 . ElogDoct: A tool for lipophilicity determination in drug discovery. 2. Basic and neutral compounds . J. Med. Chem. , 44 : 2490 – 2497 .
  • Giaginis , C. , Theocharis , S. and Tsantili‐Kakoulidou , A. 2006 . Contribution to the standardization of the chromatographic conditions for the lipophilicity assessment of neutral and basic drugs . Anal. Chim. Acta , 573–574 : 311 – 318 .
  • El Tayar , N. , van de Waterbeemd , H. and Testa , B. 1985 . Measurements of protonated basic compounds by reversed‐phase high‐performance liquid chromatography: II. Procedure for the determination of a lipophilic index by reversed‐phase high‐performance liquid chromatography . J. Chromatogr. , 320 : 305 – 312 .
  • Kaliszan , R. 1990 . High‐performance liquid‐chromatographic methods and procedures of hydrophobicity determination . Quant. Struct.‐Act. Relat. , 9 : 83 – 87 .
  • El Tayar , N. , Tsantili‐Kakoulidou , A. , Roethlisberger , T. , Testa , B. and Gal , J. 1988 . Different partitioning behaviour of sulphonyl‐containing compounds in reversed‐phase high‐performance liquid chromatography and octanol‐water systems . J. Chromatogr. , 439 : 237 – 244 .
  • Neue , U. D. , Tran , K. , Iraneta , P. C. and Alden , B. A. 2003 . Characterization of HPLC packings . J. Sep. Sci. , 26 : 174 – 186 .
  • Vervoor , R. J. , Debets , A. J. , Claessens , H. A. , Cramers , C. A. and de Jong , G. J. 2000 . Optimisation and characterisation of silica‐based reversed‐phase liquid chromatographic systems for the analysis of basic pharmaceuticals . J. Chromatogr. A , 897 : 1 – 22 .
  • Neue , U. D. 1997 . HPLC columns Weinheim : Wiley‐VCH .
  • Mendez , A. , Bosch , E. , Roses , M. and Neue , U. D. 2003 . Comparison of the acidity of residual silanol groups in several liquid chromatography columns . J. Chromatogr. A , 986 : 33 – 44 .
  • Pagliara , A. , Khamis , E. , Trinh , A. , Carrupt , P. A. , Tsai , R. S. and Testa , B. 1995 . Structural properties governing retention mechanisms on RP‐HPLC stationary phases used for lipophilicity measurements . J. Liq. Chromatogr. & Rel. Technol. , 18 : 1721 – 1745 .
  • Ascah , T. L. , Kallury , K. M.R. , Szafranski , C. A. , Corman , S. D. and Liu , F. 1996 . Characterization and high performance liquid chromatographic evaluation of a new Amide‐Functionalized Reversed Phase Column . J. Liq. Chromatogr. & Rel. Technol. , 19 : 3049 – 3073 .
  • Stella , C. , Seuret , P. , Rudaz , S. , Carrupt , P.‐A. , Gauvrit , P.‐A. , Lanteri , P. and Veuthey , J.‐L. 2002 . Characterization of chromatographic supports for the analysis of basic compounds . J. Sep. Sci. , 25 : 1351 – 1363 .
  • Neue , U. D. , Cheng , Y. F. , Lu , Z. , Alden , B. A. , Iraneta , P. C. , Phoebe , C. H. and Tran , K. 2001 . Properties of reversed phase packings with an embedded polar group . Chromatographia , 54 : 169 – 177 .
  • Layne , J. 2002 . Characterization and comparison of the chromatographic performance of conventional, polar‐embedded, and polar‐endcapped reversed‐phase liquid chromatography stationary phases . J. Chromatogr. A , 957 : 149 – 164 .
  • O'Gara , J. E. , Alden , B. A. , Walters , T. , Petersen , J. , Niederlander , C. and Neue , U. D. 1995 . Simple preparation of a C8 HPLC stationary phase with an internal polar functional group . Anal. Chem. , 67 : 3809 – 3813 .
  • Claessens , H. A. and van Straten , M. A. 2004 . Review on the chemical and thermal stability of stationary phases for reversed‐phase liquid chromatography . J. Chromatogr. A , 1060 : 23 – 41 .
  • Stella , C. , Galland , A. , Liu , X. , Testa , B. , Rudaz , S. , Veuthey , J.‐L. and Carrupt , P.‐A. 2005 . Novel RPLC stationary phases for lipophilicity measurement: Solvatochromic analysis of retention mechanisms for neutral and basic compounds . J. Sep. Sci. , 28 : 2350 – 2362 .
  • Donavan , S. F. and Pescatore , M. C. 2002 . Method for measuring the logarithm of the octanol–water partition coefficient by using short octadecyl–poly(vinyl alcohol) high‐performance liquid chromatography columns . J. Chromatogr. A , 952 : 47 – 61 .
  • Supelco 2001 catalog, Bellefonte, PA, USA 16823 http://www.sigmaaldrich.com)
  • Liu , X. , Tanaka , H. , Yamauchi , A. , Testa , B. and Chuman , H. 2004 . Lipophilicity measurement by reversed‐phase high‐performance liquid chromatography (RP‐HPLC): A comparison of two stationary phases based on retention mechanisms . Helv. Chim. Act. , 87 : 2866 – 2876 .
  • Cimpan , G. , Irimie , F. , Gocan , S. and Claessens , H. A. 1998 . Role of stationary phase and eluent composition on the determination of log P values of N‐hydroxyethylamide of aryloxyalkylen and pyridine carboxylic acids by reversed‐phase high‐performance liquid chromatography . J. Chromatogr. B , 714 : 247 – 261 .
  • Karger , B. L. , Gant , J. , Hartkopf , A. and Weiner , P. H. 1976 . Hydrophobic effects in reversed‐phase liquid chromatography . J. Chromatogr. , 128 : 65 – 78 .
  • Buckenmaier , S. M.C. , McCalley , D. V. and Euerby , M. R. 2004 . Determination of ionisation constants of organic bases in aqueous methanol solutions using capillary electrophoresis . J. Chromatogr. A , 1026 : 251 – 259 .
  • Espinosa , A. , Bonsch , E. and Roses , M. 2002 . Retention of ionizable compounds in high‐performance liquid chromatography. 14. Acid‐base pK values in acetonitrile‐water mobile phases . J. Chromatogr. A , 964 : 55 – 66 .
  • Espinosa , A. , Bonsch , E. and Roses , M. 2002 . Retention of ionizable compounds on HPLC. IX. Modeling in reversed phase liquid chromatography as a function of pH and solvent composition with acetonitrile‐water mobile phase . J. Chromatogr. A , 947 : 47 – 58 .
  • Tsantili‐Kakoulidou , A. , El Tayar , N. , Van De Waterbeemd , H. and Testa , B. 1987 . Structural effects in the lipophilicity of di‐ and polysubstituted benzenes as measured by reversed‐phase high‐performance liquid chromatography . J. Chromatogr. , 389 : 33 – 45 .
  • Minick , D. J. , Frenz , J. H. , Patrick , M. A. and Brent , D. A. 1988 . A comprehensive method for determining hydrophobicity constants by reversed‐phase high‐performance liquid chromatography . J. Med. Chem. , 31 : 1923 – 1933 .
  • Hansch , C. and Leo , A. 1995 . Exploring QSAR Vol. 2 , Washington DC : ACA .
  • Ruiz‐Angel , M. J. , Card‐Broch , S. and Berthod , A. 2006 . Ionic liquids versus triethylamine as mobile phase additives in the analysis of β‐blockers . J. Chromatogr. A , 1119 : 202 – 208 .
  • Marszall , M. P. , Baczek , T. and Kaliszan , R. 2005 . Reduction of silanophilic interactions in liquid chromatography with the use of ionic liquids . Anal. Chim. Acta , 547 : 172 – 178 .
  • Kaliszan , R. , Marszałł , M. P. , Jan Markuszewski , M. , Baczek , T. and Pernak , J. 2004 . Suppression of deleterious effects of free silanols in liquid chromatography by imidazolium tetrafluoroborate ionic liquids . J. Chromatogr. A , 1030 : 263 – 271 .
  • Schoenmakers , P. J. , Billiet , H. A.H. and de Galan , L. 1983 . Description of solute retention over the full range of mobile phase compositions in reversed‐phase liquid chromatography . J. Chromatogr. , 282 : 107 – 121 .
  • Tate , P. A. and Dorsey , J. G. 2004 . Column selection for liquid chromatographic estimation of the k′w hydrophobicity parameter . J. Chromatogr. A , 1042 : 37 – 48 .
  • Valko , K. , Snyder , L. R. and Glajch , G. L. 1993 . Retention in reversed‐phase liquid chromatography as a function of mobile‐phase composition . J. Chromatogr. A , 656 : 501 – 520 .
  • Shoenmakers , P. J. , Billiet , H. A.H. and de Galan , L. 1979 . Influence of organic modifiers on the rentention behaviour in reversed‐phase liquid chromatography and its consequences for gradient elution . J. Chromatogr. , 185 : 179 – 195 .
  • Hsieh , M. M. and Dorsey , J. G. 1993 . Accurate determination of logkw in reversed‐phased liquid chromatography . J. Chromatogr. A , 631 : 63 – 78 .
  • Unger , S. H. , Cook , J. R. and Hollenberg , J. S. 1978 . Simple procedure for determining octanol‐aqueous partition, distribution, ionization coefficients by reversed‐phase high performance liquid chromatography . J. Pharm. Sci. , 67 : 1364 – 1367 .
  • Unger , S. H. and Chiang , G. H. 1981 . Octanol‐physiological buffer distribution coefficients of lipophilic amines by reversed‐phase high‐performance liquid chromatography and their correlation with biological activity . J. Med. Chem. , 24 : 262 – 270 .
  • Lombardo , F. , Shalaeva , M. Y. , Bissett , B. D. and Christokhodova , N. 2006 . “ Physicochemical and biological profiling in drug research. ElogD7.4 20 000 compounds later: Refinements, observations and applications ” . In Pharmacokinetic Profiling in Drug Research Edited by: Testa , B. , Kramer , S. D. , Wunderli‐Allenspach , H. and Folkers , G. 187 – 201 . Zurich : Wiley‐VCH .
  • Horvath , C. , Melander , W. and Molnar , I. 1976 . Solvophobic interactions in liquid chromatography with nonpolar stationary phases . J. Chromatogr. , 125 : 129 – 156 .
  • Valko , K. and Slegel , P. 1993 . New chromatographic hydrophobicity index (φ0) based on the slope and the intercept of the log k′ versus organic phase concentration plot . J. Chromatogr. , 631 : 69 – 61 .
  • Valko , K. , Bevan , C. and Reynolds , D. 1997 . Chromatographic hydrophobicity index by fast‐gradient RP‐HPLC: A high‐throughput alternative to log P/log D . Anal. Chem. , 69 2022--2029
  • Du , C. M. , Valko , K. , Bevan , C. , Reynolds , D. and Abraham , M. H. 1998 . Rapid gradient RP‐HPLC method for lipophilicity determination: A solvation equation based comparison with isocratic . Methods. Anal. Chem. , 70 : 4228 – 4234 .
  • Valko , K. 2004 . Application of high‐performance liquid chromatography based measurements of lipophilicity to model biological distribution . J. Chromatogr. A. , 1037 : 299 – 310 .
  • Canals , I. , Valkó , K. , Bosch , E. , Hill , A. P. and Rosés , M. 2001 . Retention of ionizable compounds on HPLC. 8. Influence of mobile‐phase pH change on the chromatographic retention of acids and bases during gradient elution . Anal. Chem. , 73 : 4937 – 4945 .
  • Espinosa , S. , Bosch , E. , Roses , M. and Valko , K. 2002 . Change of mobile phase pH during gradient reversed‐phase chromatography with 2,2,2‐trifluoroethanol‐water as mobile phase and its effect on the chromatographic hydrophobicity index determination . J. Chromatogr. A. , 954 : 77 – 87 .
  • Taillardat‐Bertschinger , A. , Carrupt , P. A. , Barbato , F. and Testa , B. 2003 . Immobilized artificial membrane HPLC in drug research . J. Med. Chem. , 46 : 655 – 665 .
  • Markovich , R. J. , Stevens , J. M. and Pidgeon , C. 1989 . Fourier transform infrared assessed of membrane lipids immobilized to silica: leaching and stability of immobilized artificial membrane–bonded phase . Anal. Biochem. , 182 : 237 – 244 .
  • Barbato , F. , di Martino , G. , Grunetto , G. and La Rotonda , M. I. 2004 . Prediction of drug‐membrane interactions by IAM‐HPLC: Effects of different phospholipid stationary phases on the partition of bases . Eur. J. Pharm. Sci. , 22 : 261 – 269 .
  • Morse , K. and Pidgeon , C. 2001 . “ Importance of mobile phase in immobilized artificial membrane chromatography ” . In Pharmacokinetic Optimization in Drug Research Edited by: Testa , B. , van de Waterbeemd , H. , Folkers , G. and Guy , R. 351 – 381 . Weinheim : Verlag Helvetica Chimica Acta, Zürich and Wiley-VCH .
  • Rhee , D. , Markovich , R. , Chae , W. G. , Qiu , X. and Pidgeon , C. 1994 . Chromatographic surfaces prepared from lyse phosphatidylcholine ligands . Anal. Chim. Acta , 297 : 377 – 386 .
  • Taillardat‐Bertschinger , A. , Galland , A. , Carrupt , P. A. and Testa , B. 2002 . Immobilized artificial membrane (IAM)‐HPLC: proposed guidelines for technical optimization of retention measurements . J. Chromatogr. A , 953 : 39 – 53 .
  • Ong , S. and Pidgeon , C. 1995 . Thermodynamics of solute partitioning into immobilized artificial membranes . Anal. Chem. , 67 : 2119 – 2128 .
  • Taillardat‐Bertschinger , A. , Martinet , C. A.M. , Carrupt , P.‐A. , Reist , M. , Caron , G. , Fruttero , R. and Testa , B. 2002 . Molecular factors influencing retention on immobilized artifical membranes (IAM) compared to partitioning in liposomes and n‐octanol . Pharm. Res. , 19 : 729 – 737 .
  • Barbato , F. , di Martino , G. , Grumetto , L. and La Rotonda , M. I. 2005 . Can protonated beta‐blockers interact with biomembranes stronger than neutral isolipophilic compounds? A chromatographic study on three different phospholipid stationary phases (IAM‐HPLC) . Eur. J. Pharm.Sci. , 25 : 379 – 386 .
  • Vrakas , D. , Giaginis , C. and Tsantili‐Kakoulidou , A. 2006 . Different retention behaviour of structurally diverse basic and neutral drugs in immobilized artificial membrane (IAM) and reversed‐phase HPLC. Comparison with octanol‐water partitioning . J. Chromatogr. A , 1116 : 158 – 164 .
  • Ottiger , C. and Wunderli‐Allenspach , H. 1999 . Immobilized artificial membrane (IAM)‐HPLC for partition studies of neutral and ionized acids and bases in comparison with the liposomal partition system . Pharm. Res. , 16 : 643 – 650 .
  • Barbato , F. 2006 . The use of immobilised artificial membrane (IAM) chromatography for determination of lipophilicity . Curr. Comp.–Aid. Drug Design , 2 : 341 – 352 .
  • Lazaro , E. , Rafols , C. , Abraham , M. H. and Roses , M. 2006 . Chromatographic estimation of drug disposition properties by neans of IAM and C18 columns . J. Med. Chem. , 48 : 4861 – 4870 .

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.