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Biomedical subjects

W J Underberg

Publications and source records attributed to W J Underberg.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effect of cyclodextrins on anthracycline stability in acidic aqueous media.

The effect of cyclodextrins on the stability of six anthracyclines in acidic medium at 50 degrees C has been investigated using a stability-indicating high pressure liquid chromatographic method. The influences of various parameters, such as the structure of cyclodextrins (alpha-cyclodextrin, beta-cyclodextrin, dimethyl-beta-cyclodextrin and gamma-cyclodextrin) and anthracyclines, cyclodextrin concentration, the pH and the presence of a co-solvent, are investigated. Lineweaver-Burk plots were used to calculate the stability constants of the various inclusion complexes as well as the rate constants for degradation of the anthracycline guest molecules in the complexes with the host cyclodextrins. Anthracyclines complexate only with gamma-cyclodextrin to a substantial extent. On complexation the stability of the guest molecule increases, however, the degradation pattern does not alter. The influence of the pH on the degradation of the included molecule is identical to that of the free drug. Addition of co-solvents, such as acetonitrile, causes decomposition of the complex.

Antibiotics, Antineoplastic↗
PubMed1988

High-performance liquid chromatographic bioanalysis of anthracycline cytostatic drugs.

In the past decade high-performance liquid chromatography (HPLC) has developed into the most powerful tool available for the analysis of anthracycline antitumour drugs in all kinds of biological matrices. The results of drug level monitoring studies have contributed significantly to a better understanding of the pharmacokinetics and metabolic disposition of these drugs. Some aspects of anthracycline HPLC analysis in plasma samples are discussed, including the chromatographic separation and detection, sampling procedures, storage of plasma samples and sample pre-treatment.

Journal Article↗
PubMed1986

Anthracycline antitumour agents. A review of physicochemical, analytical and stability properties.

A review of physicochemical and analytical properties of anthracycline antitumour agents is presented. The following subjects are discussed: protolytic equilibria, partition and partition coefficients, self-association, adsorptive properties, metal complexation, spectroscopy and chromatography. Furthermore, the stability of anthracyclines in solutions, in pharmaceutical preparations and in biological media is discussed.

Adsorption↗
PubMed1986

High-performance liquid chromatographic analysis of basic compounds on non-modified silica gel and aluminium oxide with aqueous solvent mixtures.

A comparison is made between the use of aluminium oxide and non-modified silica gel as cation-exchange materials for the separation of basic drugs (amines) with aqueous solvent mixtures. The retention behaviour of the amines is studied and appears to be controlled predominantly by the pH and the concentration and nature of the modifier; the nature and concentration of the competing ions and the buffer components of the mobile phase also exert some influence on the retention. Preparations with imidazoline and tetracycline derivatives have been analysed as examples of the application of these ion-exchange systems on non-modified silica gel and aluminium oxide in the analysis of pharmaceutical formulations.

Aluminum Oxide↗
PubMed1986

Mitomycin antitumour agents: a review of their physico-chemical and analytical properties and stability.

The review enumerates the physico-chemical and analytical properties of mitomycin antitumour antibiotics, of which mitomycin C is the most important representative. After a short overview of the position of the compounds in oncology the following subjects will be discussed: structural features, prototropic properties, spectroscopy (UV-VIS, ORD, CD, IR, NMR, MS), chromatography and electrochemistry. The chemical stability and aspects of the mechanism of action of the compounds are also discussed. The last part of the review surveys the analysis of mitomycin C in biological fluids.

Journal Article↗
PubMed1986

Suppression of migration inhibition factor (MIF) production by mitomycins in vitro.

The effects of a series of mitomycins in a modified version of the Migration Inhibition Factor (MIF) test were investigated. This modified assay, which uses monocytes of the mouse cell line WEHI3 as target cells for MIF, discriminates between effects on the migrating monocytes, the production of MIF by lymphocytes and the activity of the produced MIF. The 7-methoxy mitomycins were found to be more active than the 7-amino and 7-hydroxy derivatives in suppressing both the spontaneous migration of target monocytes and the MIF production by lymphocytes. Neither of the compounds had a significant effect on the activity of produced MIF. A relationship between the activities of the mitomycins and their lipophilicity and polarographic half-wave potential is discussed. Further attention is paid to the stability of the mitomycins under the test conditions and additional advantages of the modified MIF assay over related in vitro tests for cell-mediated immunity.

Animals↗
PubMed1986

Stability of intravenous admixtures of doxorubicin and vincristine.

The stability of doxorubicin and vincristine in admixtures containing both drugs in 0.9% sodium chloride injection, 0.45% sodium chloride and Ringer's acetate injection, and 0.45% sodium chloride and 2.5% dextrose injection was studied. Doxorubicin hydrochloride was added to 30-mL quantities of each base solution to achieve initial doxorubicin concentrations of 1.40 mg/mL and to 0.9% sodium chloride injection to achieve concentrations of 1.88 and 2.37 mg/mL. Vincristine sulfate was added to each doxorubicin admixture to achieve vincristine concentrations of 0.033 and 0.053 mg/mL. All admixtures were protected from light and stored in polysiloxan bags that are used with portable delivery devices. Admixtures were kept at temperatures of 25, 30, and 37 degrees C. Samples withdrawn immediately after preparation and at 1, 2, 4, 7, 10, and 14 days were analyzed by high-performance liquid chromatography for content of each drug. The stability of doxorubicin was dependent on temperature and composition of the base solution. Analysis of data from the samples containing 0.45% sodium chloride and Ringer's acetate injection showed that doxorubicin concentrations were less than 90% of the initial concentration by 12 hours at 37 degrees C, 35 hours at 30 degrees C, and 62 hours at 25 degrees C, and visual changes occurred in all of these admixtures over the course of the study. Vincristine degradation also was most rapid in 0.45% sodium chloride and Ringer's acetate admixtures. Data analysis showed that concentrations of vincristine were less than 90% of initial after eight days at 25 degrees C, five days at 30 degrees C, and three days at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1985

Aspects of the chemical stability of doxorubicin and seven other anthracyclines in acidic solution.

The degradation of doxorubicin in acidic medium has been investigated using a stability indicating high pressure liquid chromatographic assay. Influences of temperature, pH and ionic strength on the degradation rate are quantified. The stability of doxorubicin at 50 degrees C is compared with those of seven related anthracyclines. The aglycone degradation products are characterized by mass spectrometry and by chromatography.

Antibiotics, Antineoplastic↗
PubMed1985

Quantitative aspects of the degradation of mitomycin C in alkaline solution.

The alkaline hydrolysis of mitomycin C has been studied over a wide range of pH/H_(7-15). A stability-indicating high-performance liquid chromatographic (HPLC) method was used to separate the degradation products from the parent drug. The quantitative effects of temperature and buffers on the degradation of mitomycin C in alkali have been determined. A profile of log k(obs) against pH/H_ was constructed after corrections had been made for buffer effects and after extrapolation to 25 degrees C by application of the Arrhenius equation.

Journal Article↗
PubMed1985

Qualitative aspects of the degradation of mitomycins in alkaline solution.

The major degradation product in alkaline solution of mitomycin A, mitomycin C and porfiromycin is the corresponding 7-hydroxymitosane. The isolation and the physico-chemical and analytical properties of these compounds and their derivatized analogues are discussed. Data are presented on the degradation of mitomycin C at extremely high pH values.

Journal Article↗
PubMed1983

Aspects of the chemical stability of mitomycin and porfiromycin in acidic solution.

Aspects of the degradations of mitomycin and porfiromycin were studied. The initial degradation processes of the compounds in an acidic medium were investigated. Influences of pH, buffers, and other additives such as halogenides and dioctyl sodium sulfosuccinate [sodium 1,4-bis(2-ethylhexyl)sulfosuccinate] were studied. The hydrogen ion catalyzes the degradation of both the uncharged and the protonated species. Anions also promote the degradation of the compounds in an acidic medium. Rate constants for all of the catalytic reactions could be determined. From the pH profiles, after correction for buffer influences, accurate pKa values for the aziridine nitrogens could be obtained. The protective influence of the dioctyl sulfosuccinate ion could be explained. From the data obtained a plausible mechanism for the initial acidic degradation reactions was developed.

Drug Stability↗
PubMed1978

Oxidative degradation of pharmaceutically important phenothiazines I: Isolation and identification of oxidation products of promethazine.

The thermal degradation of promethazine in water in the presence of oxygen was studied. After degradation, the products were isolated by TLC. Identification was carried out by comparison of the isolated compounds with reference compounds. Melting points, spectral data, and polarographic and chromatographic behavior were compared. The following products were identified: 10-methylphenothiazine, phenothiazine, 3H-phenothiazine-3-one, phenothiazine 5-oxide, promethazine 5-oxide, 7-hydroxy-3H-phenothiazine-3-one, acetaldehyde, formaldehyde, and dimethylamine.

Chemical Phenomena↗
PubMed1978

Oxidative degradation pharmaceutically important phenothiazines II: Quantitative determination of promethazine and some degradation products.

Methods for the determination of promethazine and several degradation products, which can be used in kinetic studies, were developed. All determinations were carried out after isolation of the compounds by TLC. Promethazine was determined by oxidation with vanadyl sulfate in an acidic medium. The method was suitable for approximately 3 mg of the compound. 3H-Phenothiazine-3-one was determined spectrophotometrically at 492 nm in acetone. The compound could be determined in amounts of 30-40 microgram. Promethazine 5-oxide was determined spectrophotometrically using the acid dye method; 100-200 microgram could be determined. 7-Hydroxy-3H-phenothiazine-3-one could be determined spectrophotometrically at 600 nm after extraction of the other compounds from the solution. The medium had to be alkaline and contain water in a fixed ratio. The method was suitable for 15-30 microgram of the compound.

Chromatography, Thin Layer↗
PubMed1978

Oxidative degradation of pharmaceutically important phenothiazines III: Kinetics and mechanism of promethazine oxidation.

The kinetics of the thermal degradation of promethazine in an acidic medium under various conditions were investigated. The degradation of promethazine and the formation of some degradation products were studied under aerobic and anaerobic conditions. The influence of pH, metal ions such as copper(II) and iron (III), and antioxidants was investigated. In an oxygen-saturated medium, promethazine generally followed first-order kinetics. Increasing the pH increased the degradation rate to a limiting value at pH 5. Addition copper (II) increased the degradation rate over the whole process, while iron (III) caused an increase for only a short time. Ascorbic acid sometimes increased the degradation rate, while higher concentrations of hydroquinone also accelerated the degradation. Pyrosulfite did not have any influence. Under anaerobic conditions, promethazine degraded only in the presence of copper (II) and iorn (III) ions. As a result of the studies on the qualitative and quantitative aspects of the oxidation process, a mechanism for the oxidative degradation of promethazine is suggested. Promethazine 5-oxide and a number of degradation products without intact side chains are formed via a semiquinone free radical. The influence of several factors on the degradation process is discussed.

Antioxidants↗