Drug level monitoring: antidepressants.

The determination of antidepressant drugs which act by blocking neuronal uptake of biogenic amines, because of their widespread use and high toxicity, remains one of the most commonly requested drug assays in clinical laboratories. Easy to use immunoassay reagents for the estimation of these drugs are commercially available. However, immunoassays have not been universally accepted because of high probability of these reagents producing false negative and false positive results. At present, column liquid chromatography with absorbance detection and coupled with solid-phase extraction is the most viable technique for a general procedure for the identification and determination of these drugs. The technique of liquid chromatography is economical, environmental friendly since water-miscible and biodegradable solvents can be used for extraction of drugs and their chromatographic separation, and amenable to full automation. New techniques of separation, such as supercritical fluid chromatography and capillary zone electrophoresis, have not yet been applied for the determination of therapeutic concentrations of antidepressants.     

Drug residue analysis using immunoaffinity chromatography.

The background and applicability of immunoaffinity chromatographic separations and clean-up to drug residue analysis of agricultural commodities is discussed. The uses of antibody specificity for separation and concentration of drug residues are presented. Examples of immunoaffinity chromatography for the determination of residues of (1) nortestosterone and methyl testosterone in swine muscle, urine and bile; (2) chloramphenicol in swine tissue, eggs and milk; (3) clenbuterol in calf urine; (4) zeranol and beta-zearalanolin in calf urine: (5) diethylstilbestrol, dienestrol and hexestrol in calf urine are presented. Further, examples of the successful coupling of immunoaffinity separations with other chromatographic techniques such as gas chromatography and high-performance liquid chromatography are presented.     

The NCI Drug Information System. 1. System overview

An interactive computer system has been designed to handle all the data associated with the National Cancer Institute's (NCI) drug screening program. The system resides on the NIH DEC System 10 computers and allows interactive access to the entire NCI screening data system. This contains over 20 separate databases, including a chemistry file of about 400,000 structures and a biology file of approximately 1.5 million test records. New compounds and test data are added daily to the files, and the system also controls and records all the daily operations of the screening program, such as acquisition, shipping, and biological testing of chemicals.     

The NCI Drug Information System. 6. System maintenance

The NCI Drug Information System (DIS) is a collection of 24 interactively searchable databases which contain all the data associated with NCI's drug screening program. Data flow into all of these databases upon a daily basis, and maintenance procedures have been developed which provide a high degree of currency to the files. An extensive security system controls both write access and read access to the DIS and matches both to the authorization possessed by each specific user. Detailed usage statistics are collected automatically. The cost of the overall system in terms of both manpower and machine time is discussed briefly.     

The NCI Drug Information System. 2. DIS Pre-Registry

The Pre-Registry Module of the Drug Information System (DIS) is a staging area through which all new compounds are passed prior to acquisition and testing. Several methods are available for the entry of structures into the Pre-Registry; all involve built-in data validation. Newly entered structures are examined by computer programs for structural novelty and potential for anticancer activity. For those compounds that proceed to acquisition, the various acquisition steps, such as letter writing and record updating, are performed automatically. When a sample is obtained, the entire Pre-Registry record is updated and moved forward into the permanent DIS chemistry files.     

Drug detection in hair by chromatographic procedures.

This article reviews the analysis of 31 drugs and drug metabolites in human hair by thin-layer chromatography, high-performance liquid chromatography, gas chromatography, gas chromatography-mass spectrometry and mass spectrometry. The most important detection method after chromatographic separation of the components is the mass spectrometry because of its sensitivity and specificity. Washing steps to exclude external contamination, extraction, derivatization, stationary phases, detection modes and detection limits of the mass spectrometric and gas chromatographic-mass spectrometric procedures are presented in five tables. Additionally, a method for a gas chromatographic-mass spectrometric screening procedure is presented.     

The NCI Drug Information System. 5. DIS Biology Module

The NCI drug screening program tests over 10,000 chemicals per year for activity against cancer. The associated Drug Information System (DIS) captures all the raw testing data and provides for its validation. The large quantity of numeric data gathered during testing is maintained within the DIS in a database that is interactively searchable and automatically updated at regular intervals.     

The NCI Drug Information System. 3. The DIS Chemistry Module

The Chemistry Module of the Drug Information System (DIS) handles a database of 400,000 structures. New or modified records are created in this database on a daily basis and are merged into the file promptly. The Chemistry database is searchable in a wide variety of ways and provides novel methods for both input and output of chemical structures.     

The NCI Drug Information System. 4. Inventory and Shipping Modules

The Inventory/Shipping package of the NCI Drug Information System (DIS) is designed to support all inventory and shipping operations associated with the testing by the NCI of large numbers of chemicals for anticancer activity. Two major databases, an Inventory database and a Shipping History database, contain all of the data associated with these operations. Software that supports the operations in an online interactive manner also provides for the accessing and updating of these databases as necessary. Special hardware in the form of barcode reader/printers and digital balances is also interfaced to the system to improve the efficiency of the operations.     

Biosensors in Drug Discovery and Drug Analysis

Abstract

Biosensors are, by definition, sensing devices comprising a biological component (enzyme, antibody, animal or plant cell, oligonucleotide, lipid, microorganisms, etc.) intimately connected to a physical transducer (electrode, optical fiber, vibrating quartz, etc.). This dual configuration permits a quantitative study of the interaction between a drug compound and an immobilized biocomponent. Ideally, biosensors should be readily implemented and allow for low reagent and energy consumption. Enzyme‐based biosensors can be applied in the pharmaceutical industry for monitoring chemical parameters in the production process (in bioreactors). Affinity biosensors are suitable for high‐throughput screening of bioprocess‐produced antibodies and for candidate drug screening. They are suitable for selective and sensitive immunoassays in clinical laboratories and for decentralized detection of drug residues. Enzyme‐based biosensors may be used in hospitals for bedside drug testing, emergency control, in patient treatment control (anticancer therapy) etc. Current research efforts are focused on proteins, tissues, or living cells immobilized in microfabricated configurations for high‐throughput drug screening and discovery. Such devices can comprise several different microelectronic sensors and biosensors sensitive, for example, to pH, temperature, impedance, dissolved oxygen, etc. for a multiparametric monitoring. Of equal new interest are the oligonucleotide‐immobilized biosensors for interactions studies between a surface linked DNA and the target drug or for hybridisation studies. This short review summarizes several recent trends dedicated to the development and application of biosensors in the pharmaceutical arena.     

pH-Induced Difference Spectrophotometric Methods for Drug Analysis. I. Determination of Indomethacin

Abstract

On the basis of the spectral changes of indometnacin induced by changing the pH of the solvent medium, a method for its determination has been developed. The latter involves absorbance measurement of both acid and alkaline solutions of the compound at 260 nm: the difference between both values is linearly related to concentration in the range 0.4-1.4 mg/100 ml. The mean percentage recovery of authentic samples equal 100.1±0.42 (p=0.05). The method has been applied to the analysis of pharnaceutical preparations; the results obtained as compared to those of the official method indicate warranty of application in routine analysis.