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At least 73 records · Page 4Linked to original sources
PubMed2000

Biosensor analysis of the interaction between immobilized human serum albumin and drug compounds for prediction of human serum albumin binding levels.

The interactions between a set of drugs, selected on the basis of reported human serum albumin (HSA) binding levels, and immobilized HSA were investigated using surface plasmon resonance technology. Major HSA binding sites were available after immobilization. The intensity of the signal obtained from the interaction of the drug with the HSA surface was correlated with the reported HSA binding level. Drugs were classified into groups corresponding to high, medium, or low HSA binding based on the injection of the drug at 80 microM concentration. A set of 10 drugs binding to alpha(1)-acid glycoprotein (AGP) was also investigated and correlated with reported AGP binding data. The throughput of the presented assay is 100 compounds/24 h, and the sample consumption is less than 100 microL (8 nmol).

Binding Sites↗
PubMed1998

Simultaneous quantification of released succinic acid and a weakly basic drug compound in dissolution media.

A HPLC-method was developed to determine both fenoldopam, a weakly basic drug and succinic acid, a pH-adjuster for this drug in dissolution media. The usual assays for succinic acid were not applicable due to its low UV-absorption, the low pH-value of samples or the presence of buffer salts and fenoldopam. The described method is a simple non-ion-pair reversed phase HPLC-method using a fast scanning UV-detector and a PC software program for the quantification of both components. Succinic acid is detected at 205 nm and fenoldopam at 225 nm. The UV-spectrum is used to determine peak purity and to identify peaks (carried out at a 99.9% match). This is especially important as in some of the investigated samples an unknown peak elutes immediately after succinic acid, resulting in spurious high contents, if mistaken for succinic acid. The simple method accomplished the simultaneous quantification of both, succinic acid and fenoldopam, by an accurate, precise, specific and reproducible assay, with a linear range covering all concentrations relevant for dissolution testing. The method is stability indicating and can also be used for the quantification of fumaric acid, another pH-adjuster in dissolution media together with fenoldopam.

Chemistry, Pharmaceutical↗
PubMed1992

Stabilization by ethylenediaminetetraacetic acid of amide and other groups in drug compounds.

Ethylenediaminetetraacetic acid (EDTA) was shown to be effective in stabilizing pharmaceutical compounds, which contain acetamido groups, from degradation by light, e.g. paracetamol. Its addition is particularly effective in stabilizing such compounds from the action of ascorbic acid in the light or dark. EDTA was also shown to stabilize lignocaine, sulphadiazine and succinylsulphathiazole. Previous studies had shown that EDTA stabilizes the acetamido group present in two synthetic food colouring compounds.

Acetaminophen↗
PubMed1999

The effects of sample preparation methods on the variability of the electrospray ionization response for model drug compounds.

A post-column infusion system was developed in order to analyze suppression of electrospray ionization (ESI) tandem mass spectrometry response in the presence of endogenous plasma interferences. By enabling direct detection of these interfering components, this experimental system was used to analyze the ability of several common extraction procedures to remove endogenous plasma components that cause changes in the ESI response of model drug substances. Methyl-t-butyl ether (MTBE) liquid-liquid, Oasis and Empore solid-phase, and acetonitrile (ACN) protein precipitation sample preparation methods were tested using the post-column infusion system. In all cases, ACN protein precipitation samples showed the greatest amount of ESI response suppression while liquid-liquid extracts demonstrated the least. In addition, the three test compounds, phenacetin, caffeine, and a representative Merck compound, demonstrated that ESI response suppression is compound dependent. Suppression was greatest with caffeine, the most polar analyte, and the smallest for the Merck compound, the least polar analyte. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗
PubMedDate not supplied

[The participation of the T system and macrophages in the immediate immune response to drug compounds].

Experiments on rats and on human lymphocytes have indicated that a prompt immune response to low-molecular-weight biologically active agents is thymus-dependent, calls for cooperative interaction of T and B lymphocytes and macrophages, it is enhanced by T mitogens and implemented through the specific pharmacological receptors of T and B lymphocytes. The findings offer ample scope for controlling the immune mechanisms of habituation to drugs and poisons.

Animals↗
PubMed1992

Polymethylmethacrylate-antiblastic drug compounds: an in vitro study assessing the cytotoxic effect in cancer cell lines--a new method for local chemotherapy of bone metastasis.

An in vitro study was performed assessing the pharmacologic properties of polymethylmethacrylate (PMMA)-antiblastic agent (doxorubicin and cisplatinum) mixtures in normal and neoplastic cell lines cultures. The study's aim was to analyze the polymerization capacity of PMMA in the presence of doxorubicin and cisplatinum, the release of drug from the mixture, the kinetics of release, and the effect of the released drugs in normal and neoplastic cell cultures. Our data show that even at high concentrations neither doxorubicin nor cisplatinum inhibit the polymerization of PMMA. Moreover, mixtures in vitro can release the antiblastic drug which maintains its pharmacologic activity on sensitive neoplastic cells. Therefore, the PMMA-antiblastic drug mixtures, along with current anti-cancer therapy (systemic chemotherapy and radiation therapy), may provide better local control of the metastatic lesion and of some bone tumors.

Bone Neoplasms↗
PubMedDate not supplied

[Antimutagenic properties of a series of drug compounds].

Caffeine, hexamidine, Lm8, methionine, ATP, ionol, and vitamin E enhance the proliferation of the normal embryonic culture of human fibroblasts. Arginine, streptomycin and cysteamine exert no action on the growth of the culture. Analysis of similar effects on the culture of xeroderma pigmentosum has demonstrated that caffeine, hexamidine, Lm3 and vitamin E also enhance the proliferation of the culture. Ionol produces no effect on the culture of xeroderma pigmentosum. The mutagenic agent dioxidine causes a sharp inhibition of the proliferation of normal embryonic culture and has no effect on the culture of xeroderma pigmentosum

Cell Division↗
PubMed2000

Statistical validation of reproducibility of HPLC peptide mapping for the identity of an investigational drug compound based on principal component analysis.

Peptide mapping is a key analytical method for studying the primary structure of proteins. The sensitivity of the peptide map to even the smallest change in the covalent structure of the protein makes it a valuable "fingerprint" for identity testing and process monitoring. We recently conducted a full method validation study of an optimized reverse-phase high-performance liquid chromatography (RP-HPLC) tryptic map of a therapeutic anti-CD4 monoclonal antibody. We have used this method routinely for over a year to test production lots for clinical trials and to support bioprocess development. One of the difficulties in the validation of the peptide mapping method is the lack of proper quantitative measures of its reproducibility. A reproducibility study may include method and system precision study, ruggedness study, and robustness study. In this paper, we discuss the use of principal component analysis (PCA) to quantitate peptide maps properly using its projected scores on the reduced dimensions. This approach allowed us not only to summarize the reproducibility study properly, but also to use the method as a diagnostic tool to investigate any troubles in the reproducibility validation process.

Antibodies, Monoclonal↗
PubMed1978

A "carrier effect" observed in assay of antidiarrhoeal drug compounds.

A carrier effect has been shown to exist in a stable isotope dilution assay for diphenoxylate. When a tetradeuterated analogue is used as a carrier and internal standard a sevenfold increase in sensitivity is observed for the unlabelled compound. Examination of a related pharmacologically active compound (SC-27166) showed a much smaller effect.

Antidiarrheals↗
PubMed2004

A method for the direct analysis of drug compounds in plasma using a single restricted access material (RAM) column.

We describe an automated approach to analyzing whole plasma samples using online extraction without the need for an analytical column. A single restricted access material (RAM) column provided online extraction and pre-concentration of analytes while effectively removing proteins, salts and other biological materials found in the plasma sample matrix. The reduction in the plasma matrix enabled direct elution of the analytes from the extraction column to the mass spectrometer for selective detection. The precision of the method was evaluated using a proprietary therapeutic agent (Compound A) and was less than 5% over the range of 1-500ng/ml in spiked whole plasma, with an LOQ of 1ng/ml. A side-by-side comparison of RAM results from a pharmacokinetic study in rats was made with a traditional protein precipitation LC-MS method and a correlation of 0.993 was obtained between both methods. The injection-to-injection cycle time for the RAM method was 8min. Further automation was demonstrated by addition and mixing of the internal standard to all samples via an injection program of the autosampler.

Animals↗
PubMed1993

Polyanhydride microspheres that display near-constant release of water-soluble model drug compounds.

A new method to prepare polyanhydride microspheres capable of near-constant sustained release of low molecular weight, water-soluble molecules is presented. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. Acid orange 63 (AO), acid red 8 (AR), and p-nitroaniline, were used as model release molecules. P(FAD-SA) microspheres containing the molecules with or without gelatin were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 50-125 microns and encapsulated more than 85% of the molecule, irrespective of the compound used. Near-zero-order degradation kinetics were observed for 5 days as judged by sebacic acid (SA) release. Microsphere degradation was pH sensitive, being enhanced at high pH, and became more stable in acidic conditions, irrespective of the incorporation of gelatin in the matrix. For the gelatin-free microspheres, a close correlation of SA release and AO release was observed (2% loading), suggesting a release mechanism that was controlled dominantly by degradation. However, the incorporation of gelatin into the microsphere significantly extended the periods of molecule release from P(FAD-SA) microspheres, although the degradation profile of the microspheres themselves was quite similar to that of gelatin-free microspheres. It is possible that an interaction between FAD monomers and gelatin molecules causes continued release, even after the polymer matrix completely degrades (even after complete degradation, FAD monomers remain because of their poor water solubility). Thermal analysis of polyanhydride microspheres at different degradation stages demonstrated that a crystalline structure was formed between gelatin and the FAD monomers produced with microsphere degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry, Differential Scanning↗