[Derivative spectrophotometric and NMR spectroscopic study in pharmaceutical science].
This review starts with an introduction of derivative spectrophotometry followed by a description on the construction of a personal computer-assisted derivative spectrophotometric (DS) system. An acquisition system for inputting digitalized absorption spectra into personal computers and a BASIC program for calculating derivative spectra were developed. Then, applications of the system to drug analyses that are difficult with traditional absorption methods are described. Following this, studies on the interactions of drugs with biological macromolecules by the DS and NMR methods were discussed. An (1)H NMR study elucidated that the small unilamellar vesicle (SUV) has a single membrane made of a phosphatidylcholine bilayer, and that chlorpromazine interacts with both the outer and inner layers. (13)C NMR revealed a reduction of the dissociation constants of phenothiazine drugs due to their interaction with SUV. The partition coefficients of phenothiazine, benzodiazepine and steroid drugs in an SUV-water system and the effects of cholesterol or amino lipids content on these partition coefficients were examined by the DS method. The binding constants of phenothiazine drugs to bovine serum albumin (BSA) and the influence of Na(+), K(+), Cl(-), Br(-), and I(-) on these binding constants were determined by DS. It was found that I(-), Br(-), Cl(-) reduce the binding constants in this order, and that Na(+) and K(+) have no effect. A (19)F NMR study revealed that triflupromazine binds to BSA and human serum albumin in two regions including Site II with different populations, and that a nonsteroidal anti-inflammatory drug, niflumic acid, binds Sites Ia and Ib.
Kitamura
Keisuke
K
Kyoto Pharmaceutical University, 3 Nakauchicho, Misayagi, Yamashina-ku, Kyoto 607-8414, Japan. kitamura@mb.kyoto-phu.ac.jp
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002626:Chemistry, Pharmaceutical; D004347:Drug Interactions; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008838:Microcomputers; D009544:Niflumic Acid; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010640:Phenothiazines; D011485:Protein Binding; D012709:Serum Albumin; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008081:Liposomes; D004364:Pharmaceutical Preparations; D010640:Phenothiazines; D012709:Serum Albumin; D009544:Niflumic Acid; C031637:phenothiazine