Extraction of drugs

These enzymes (and transporters) exhibit differential expression at various sites throughout the GIT. For example, CYP3A4 expression is highest in the duodenum and lowest in the colon conversely, the expression of P-gp is greatest in the colon. This has implications for the gut wall first-pass extraction of drugs delivered by modified-release formulations, where the majority of the drug must be absorbed from the colon. 

Rindflesch TC et al. EDGAR Extraction of drugs, genes and relations from biomedical literature. Pac Symp Biocomput 2000 517-528. 

Formats for Rapid and/or High-Throughput Solid Phase Extraction of Drugs in Biological Matrices... 

Herman J.L., 2002. Generic method for online extraction of drug substances in the presence of biological matrices using turbulent flow chromatography. Rapid Commun Mass Spectrom 16 421. 

Immunoaffinity procedures can be performed either on-line or off-line, and can be coupled to chromatographic systems [ 118,119] or even to immunoassays [120]. Many examples can be found in the literature regarding the use of immunoaffinity extraction of drugs and pharmaceuticals from biological matrices, as well as of organic pollutants such as pesticides from environmental samples [115,121-124]. 

The effective and meaningful extraction of an analyte is rendered almost impossible when one encounters an emulsion formation during an extraction process thereby the separation of the two phases becomes difficult. Actually, it offers a frequent and serious problem when dealing with the extraction of drugs from biological as well as pharmaceutical formulations. 

This postulated phenomenon can have the beneficial effect of reducing the likelihood of systemic side-effects by effectively buffering the rate at which the drag enters the systemic circulation and hence reducing peak-to-trough variations in concentration. Conversely, high affinity for Hver Hssue may increase exposure to the enzymes of clearance and may therefore attenuate the first-pass extraction of drugs. 

ROBUSTNESS OF LIQUID-LIQUID EXTRACTION OF DRUGS FROM BIOLOGICAL SAMPLES... 

A systematical approach of sample preparation methods and optimisation of the quality aspects of sample preparation may enhance the efficiency of total analytical methods. This approach may also enhance the quality and knowledge of the methods developed, which actually enhances the quality of individual sample analyses. Unfortunately, in bioanalysis, systematical optimisation of sample preparation procedures is not common practice. Attention to systematical optimisation of assay methods has always been mainly on instrumental analyses problems, such as minimising detection limits and maximising resolution in HPLC. Optimisation of sample extraction has often been performed intuitively by trial and error. Only a few publications deal with systematical optimisation of liquid-liquid extraction of drugs from biological fluids [3,4,5]. 

The algorithms presented in this paper provide an alternative method for the selection of robust conditions for liquid-liquid extraction of drugs from biological fluids. The advantage of this new method is that response criteria are modelled. The models can subsequently be used to predict responses under conditions that have not been measured (by interpolation in the factor space). 

J. Wieling, Liquid-Liquid Extraction of Drugs from Biological Fluids Robotisation and Optimisation, thesis. University of Groningen, 1993. 

A 96-well SPE system for the simultaneous extraction of drugs and metabolites in biological matrices developed by Wu and coworkers (Simpson et al, 1998) is shown in Figure 6.39. In this approach, smaller elution volumes (75-200 FL) are used to improve SPE performance. This volume reduction allowed for the direct injection of samples without any evaporation and reconstitution. The collection plate that contains the elution fraction is loaded to an autosampler that is compatible with 96-well plates, thereby, eliminating the transfer to injection vials. This quantitative process improvement led to an improved analytical performance, considerable savings in time, and reduced cost. 

Koster et al. [140] conducted on-fiber derivatization for SPME to increase the detectability and extractability of drugs in biological samples. Amphetamine was used as a model compound. The extraction was performed by direct immersion of a 100-pm polydimethylsiloxane-coated fiber into buffered human urine. On-fiber derivatization was performed with pentafluorobenzoyl chloride either after or simultaneously with extraction. 

Considerable research has been directed toward understanding the effect of potent CYP3A inhibitors on the first-pass extraction of drugs at both the... 

The chemical composition of the matrix can have either a positive or a negative effect on the results obtained by SFE. One of the most important parameters influencing the extraction is the degree of humidity of the sample. For example, it is generally admitted that a partial dehydration of the sample allows for a faster extraction. Indeed, hydrophylic matrices have a tendency of preventing contact between the supercritical fluid and the analyte. This is particulary true for the extraction of drugs from skin tissue. In specific cases, however, the presence of water can, on the contrary, improve the rate of extraction by acting as an "internal cosolvent."... 

It was Sachs and UhT" and Sachs and RafF in 1992-3 that demonstrated for the first time the use of supercritical fluids in the extraction of drugs in hair. They illustrated the possibility of extracting opiates and cocaine in hair by means of a mixture of COj-ethyl acetate. The recovery of the extraction as well as the reproducibility of the method, however, remain inferior to other conventional techniques. Two years later, Edder et al., demonstrated the quantitative extraction of opiates in hair, and Morrison et al. the quantitative extraction of cocaine. The results presented in this chapter are therefore a synthesis of these two works. 

The results presented in this chapter demonstrate that a polar modifier (MeOH, TEA, HjO) should be added to the CO2 in order to extract drugs accumulated in hair. On the other hand, CO2 by itself permits the extraction of drugs slightly adsorbed on the surface of hair. It then becomes possible by SFE to distinguish between drugs remaining on the surface, or left by outside contamination, and those incorporated in the hair. 

Curcuruto, O., Guidugli, R, Traidi, R, Sturaro, A., Tagliaro, F., and Marigo, M., Ion-trap mass spectrometry applications in forensic sciences. I. Identification of morphine and cocaine in hair extracts of drug addicts. Rapid Commm. Mass Spectrom., 6, 434, 1992. 

Scheme for the extraction of drugs from urine and stomach contents... 

J Scheurer, CM Moore. Solid-phase extraction of drugs from biological tissues. J Anal Toxicol 16 264-269, 1992. 

Herman, J.L. "Generic Method for On-Line Extraction of Drug Substances in the P esence of Biological Matrices Using Turbulent Flow Chromatography, Rapid Commun. Mass Spectrom. 16,42 W26 (2002). 

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