Biomaterial Database

Relationship between immobilized artificial membrane chromatographic retention and human oral absorption of structurally diverse drugs. 2007

Jignesh Kotecha, and Shailesh Shah, and Ishwarsinh Rathod, and Gunta Subbaiah

Department of Quality Assurance, L.M. College of Pharmacy, P.O. Box 4011, Navrangpura, Ahmedabad 380009, India.

Capacity factors are determined for a set of drugs for which human oral absorption (HOA) data are available, using immobilized artificial membrane (IAM) chromatography. The compound set represented acidic, basic, neutral and amphoteric drugs from various structure classes and having low to high human oral absorption. Effect of mobile phase pH on retention was investigated to determine the optimal condition for better correlation with HOA. The retention (capacity factor, k'(IAM) of each drug was measured by reverse phase HPLC using an IAM.PC.DD2 (1 cm x 3 mm i.d., 12 microm) column with an eluent of acetonitrile - 0.01 M phosphate buffer at pH 4.5-7.4. The pH dependent k'(IAM) was in accordance with pH partition theory. Using non-linear regression analysis the obtained log k'(IAM) values were compared with published data on HOA in order to establish correlation. The better correlation with HOA was observed when the highest log k'(IAM) value selected among pH 4.5-7.4 (R(2)=0.8566) for each drug rather than obtained at more traditional pH 7.4 (R(2)=0.7403). Finally, it was confirmed by Cook's D outlier test that there was no influential observation in the model that affect the relationship between IAM capacity factor and HOA. The assay conditions were optimized and validated to make it suitable for routine analysis and for compound characterization in early discovery where permeability may be an issue.

UI	MeSH Term	Description	Entries
D007408	Intestinal Absorption	Uptake of substances through the lining of the INTESTINES.	Absorption, Intestinal
D008567	Membranes, Artificial	Artificially produced membranes, such as semipermeable membranes used in artificial kidney dialysis (RENAL DIALYSIS), monomolecular and bimolecular membranes used as models to simulate biological CELL MEMBRANES. These membranes are also used in the process of GUIDED TISSUE REGENERATION.	Artificial Membranes,Artificial Membrane,Membrane, Artificial
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D010539	Permeability	Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.	Permeabilities
D011237	Predictive Value of Tests	In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.	Negative Predictive Value,Positive Predictive Value,Predictive Value Of Test,Predictive Values Of Tests,Negative Predictive Values,Positive Predictive Values,Predictive Value, Negative,Predictive Value, Positive
D012044	Regression Analysis	Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable.	Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
D002851	Chromatography, High Pressure Liquid	Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.	Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004058	Diffusion	The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially FACILITATED DIFFUSION, is a major mechanism of BIOLOGICAL TRANSPORT.	Diffusions
D004364	Pharmaceutical Preparations	Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.	Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical