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Biomedical subjects

W J Underberg

Publications and source records attributed to W J Underberg.

At least 55 records · Page 3Linked to original sources
PubMed1993

Hydrolysis of saturated soybean phosphatidylcholine in aqueous liposome dispersions.

Hydrolysis kinetics of saturated soybean phosphatidylcholine (PC) were investigated as a function of pH, temperature, buffer concentration, buffer species, and ionic strength in aqueous liposome dispersions. A high-performance liquid chromatography method was used to separate PC and the hydrolysis products. Hydrolysis of PC followed pseudo first-order kinetics. Hydrolysis of fatty acid esters at sn-1 and sn-2 positions initially resulted in the formation of 2-acyl lyso-phosphatidylcholine and 1-acyl lyso-phosphatidylcholine; because of acyl migration, the most stable isomer of lyso-phosphatidylcholine, 1-acyl lyso-phosphatidylcholine, was formed predominantly. General acid-base catalysis was observed for acetate and Tris ions. The pH profiles at 40 and 70 degrees C for a buffer concentration of 0.05 M showed a minimum hydrolysis rate at about pH 6.5. The relationship between the observed rate constant and temperature could be described adequately by the Arrhenius equation below and above the phase transition temperature of saturated soybean PC (52 degrees C).

Buffers↗
PubMed1993

2',3'-dideoxyinosine (ddI): its chemical stability and cyclodextrin complexation in aqueous media.

The chemical stability of 2',3'-dideoxyinosine has been studied over a wide pH range (0-12). A stability-indicating HPLC method was used to separate the degradation product from the parent drug. The effects of temperature, ionic strength and buffer components on the degradation kinetics were investigated. Furthermore, the influence of some cyclodextrins (alpha-, beta-, HP-beta-, DM-beta- and gamma-cyclodextrin) on the drug stability have been studied.

Buffers↗
PubMed1993

Hydrolysis of partially saturated egg phosphatidylcholine in aqueous liposome dispersions and the effect of cholesterol incorporation on hydrolysis kinetics.

Hydrolysis kinetics of partially hydrogenated egg phosphatidylcholine (PHEPC) were studied as a function of pH, temperature, buffer concentration, ionic strength, and the effect of cholesterol incorporation. Results showed that PHEPC has a maximum stability at around pH 6.5. General acid base catalysis was observed for acetate, HEPES and Tris buffers. Increasing the ionic strength of the buffer solutions did not influence the hydrolysis kinetics. The relationship between the observed hydrolysis rate constants and the temperature could adequately be described by the Arrhenius equation. Incorporation of cholesterol did not affect the hydrolysis kinetics. This result indicates that the hydrolysis kinetics of PHEPC do not depend on the changes in bilayer rigidity induced by cholesterol incorporation. Cholesterol is stable under the experimental conditions used in this study; no changes were observed in cholesterol concentration over the experimental time interval.

Buffers↗
PubMed1992

Gas chromatographic determination of 2- and 3-dechloroethylifosfamide in plasma and urine.

The metabolic oxidation of one of the chloroethyl groups of the antitumour drug ifosfamide leads to the formation of the inactive metabolites 2- and 3-dechloroethylifosfamide together with the neurotoxic metabolite chloroacetaldehyde. A very sensitive capillary gas chromatographic method, requiring only 50 microliters of plasma or urine, has been developed to measure the amounts of the drug and the two inactive metabolites in a single run. Calibration curves were linear (r > 0.999) in the concentration ranges from 50 ng/ml to 100 micrograms/ml in plasma and from 100 ng/ml to 1 mg/ml in urine.

Chromatography, Gas↗
PubMed1992

Platinum antitumour agents: a review of (bio)analysis.

This paper summarizes analytical techniques in order to get a clear picture of the ins and outs of the (bio)analysis of platinum-containing compounds. The antitumour agent cisplatin has become an indispensable drug for the cure of a variety of cancer diseases. Since its introduction in the early seventies, about 2,000 related platinum complexes were designed to devoid the dose-limiting nephrotoxicity. Some of them were introduced for clinical trial, such as carboplatin and iproplatin. To investigate the mechanism of action and pharmaco-kinetic behaviour, several interesting assays for total and specific platinum determination in biological matrices have been developed, each with its own possibilities and limitations.

Animals↗
PubMed1991

Gas chromatographic determination of ifosfamide in microvolumes of urine and plasma.

In oncology, particularly in pediatric malignancies, high doses (5-10 g/m2) of the oxazaphosphorine ifosfamide play an important role in the treatment of sarcomas. Pharmacokinetic data of ifosfamide and its metabolites in these cases are scanty. Considering the special demands of the determination of ifosfamide in plasma of young children, a very sensitive capillary gas chromatographic method, requiring only 50 microliters of plasma, has been developed. This bioanalysis of ifosfamide shows good linearity and accuracy in the concentration range 10 ng to 100 micrograms per ml of plasma and 25 ng to 1 mg per ml of urine. The absolute limits of detection in plasma and urine are 2 ng/ml and 5 ng/ml, respectively. The stability of various solutions of ifosfamide and trofosfamide was tested and proved to be satisfactory, except for ifosfamide in plasma and urine kept in the refrigerator. The validity of the method for pharmacokinetic purposes is shown in the case of one patient.

Antineoplastic Agents↗
PubMed1991

HPLC determination of doxorubicin, doxorubicinol and four aglycone metabolites in plasma of AIDS patients.

A high-performance liquid chromatographic (HPLC) assay has been developed for the determination of the anticancer drug doxorubicin and the metabolites doxorubicinol, doxorubicinone, 7-deoxydoxorubicinone, doxorubicinolone and 7-deoxydoxorubicinolone in plasma of AIDS patients. Samples can be heated at 60 degrees C for 30 min to inactivate the human immunodeficiency virus. The sample pre-treatment involves a liquid-liquid extraction of the buffered plasma sample (pH 9) with a chloroform-1-propanol (4:1, v/v) mixture. The chromatographic analysis is performed on a Lichrosorb RP-8 (5 microns) column and by isocratic elution with a mobile phase of acetonitriletetrahydrofuran-phosphate buffer (pH 2.2) (800:5:200, w/w/w) with fluorescence detection (excitation wavelength: 460 nm; emission wavelength: 550 nm). The proposed method has been validated and, subsequently, implemented in a pharmacokinetic study of doxorubicin in AIDS patients with Kaposi's sarcoma who are treated with the combination regimen doxorubicin, vincristine and bleomycin.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Effect of cyclodextrins on the chemical stability of mitomycins in alkaline solution.

The effects of cyclodextrins on the chemical stability of several mitomycin antibiotics in an alkaline medium have been investigated. A stability-indicating high-performance liquid chromatographic method was used to determine the overall degradation rate constants. The influence of various parameters such as structural variations of the cyclodextrins and mitomycins, temperature and pH was studied. It appears that complexation is most favourable with gamma-cyclodextrin. All mitomycin-gamma-cyclodextrin complexes degrade at lower rates than those of the free drugs. Moreover, it was shown that gamma-cyclodextrin influences the equilibrium between mitomycin C and its zwitterion mesomer.

Alkalies↗
PubMed1991

A systematic study on the chemical stability of ifosfamide.

The degradation kinetics of ifosfamide in aqueous solution have been investigated over the pH region 1-13 at 70 degrees C. A stability indicating high-performance liquid chromatographic assay with UV detection was used to separate degradation products from the parent compound. The degradation kinetics were studied as related to pH, buffer composition, ionic strength, temperature and drug concentration. A pH-rate profile at 70 degrees C, obtained from (pseudo) first-order kinetic plots, was constructed after corrections for buffer effects were made. The degradation reactions of ifosfamide were found to be largely independent of pH, although proton or hydroxyl catalysis occurs at extreme pH values. Ifosfamide shows maximum stability in the pH region 4-9, corresponding to a half-life of 20 h.

Buffers↗
PubMed1990

The risks of handling cytotoxic drugs. I. Methods of testing exposure.

Results of various biological and physical/chemical tests of the urines or blood of health-care personnel working with cytotoxic drugs are discussed. The outcomes of these tests are conflicting and inconclusive. The physical/chemical tests seem to be an alternative method. However, until now it has not been possible to establish the threshold concentration in urine or blood beneath which no effect has to be expected. Therefore, the interpretation of the concentration of cytotoxic drugs and/or the metabolites in the urine or blood is difficult. As long as one will not be able to provide conclusive data on the health hazards when working with cytotoxic drugs, protective measures have to be taken in order to lower the risk as much as possible.

Antineoplastic Agents↗
PubMed1990

The risks of handling cytotoxic drugs. II. Recommendations for working with cytotoxic drugs.

Presuming that preparation of antineoplastic drugs without proper protection may lead to mutagenic urine (of which the effects are uncertain), one has to take great care when preparing these drugs. Apart from Norway no other country has national regulations issued by the government for handling cytostatic agents. Many organizations in various countries have made their own guidelines, which may be adapted to the situations in local hospitals. The following recommendations have been compiled after a review of the literature. They reflect a personal set of guidelines for preparation, administration and disposal of cytotoxic drugs. They are probably the minimum precautions that should be taken, and have not been approved by any committee or agency. Further precautions must first have their potential benefit weighed against probable inconvenience and additional costs.

Antineoplastic Agents↗
PubMed1990

Inclusion complexation of doxorubicin and daunorubicin with cyclodextrins.

The interaction of alpha-, beta- and gamma-cyclodextrins with the anthracycline antibiotics doxorubicin and daunorubicin was investigated by LC, circular dichroism (CD) and absorption spectroscopy. All studies were performed in aqueous media at different temperatures and pH values. The anthracyclines complex only with gamma-cyclodextrin. Lineweaver-Burk and Scott's plots were used to calculate the stability constants of the anthracycline-gamma-cyclodextrin inclusion complexes.

Chromatography, High Pressure Liquid↗
PubMed1990

Equilibrium kinetics of the new experimental anti-tumour compound SK&F 104864-A in aqueous solution.

The equilibrium kinetics of lactone ring hydrolysis in the new experimental anti-tumour compound SK&F 104864-A. (S)-dimethylaminomethyl-10-hydroxycamptothecin hydrochloride, have been studied. Only one product is formed, SK&F 105992. A stability-indicating HPLC method has been optimized to perform the analysis. The pH is the main factor influencing equilibrium; at pH greater than or equal to 10 the lactone ring is quantitatively opened while at pH values less than or equal to 4 the lactone form is exclusively present. Other parameters, such as buffer ions and ionic strength, do not influence equilibrium. Complexation with dimethyl-beta-cyclodextrin stabilizes the lactone form. Other cyclodextrins do not show this stabilization.

Camptothecin↗
PubMed1990

High-performance liquid chromatographic analysis of the new antitumour drug SK&F 104864-A (NSC 609699) in plasma.

A high-performance liquid chromatographic (HPLC) assay is described for the determination of the new, investigational antitumour drug SK&F 104864-A and its lactone ring opened form (SK&F 105992). The analytical methodology reported here involves a protein precipitation step with methanol as sample pretreatment procedure. The instability of the drug necessitates that the plasma fraction is obtained within 5 min after blood sampling by centrifugation, immediately followed by protein precipitation with cold methanol (-30 degrees C). The methanolic extract can be stored at -30 degrees C for several days without deterioration of the analyses. Stability data of the drug and its lactone ring opened metabolite in plasma and after methanolic extraction are discussed. The parent drug and the metabolite are separated by reversed-phase ion-pair liquid chromatography on a LiChrosorb RP-18 column, using methanol-water eluent (pH 6.0) with sodium dioctylsulphosuccinate (DOSS) as ion-pairing agent and fluorescence detection. The proposed method has been validated and, subsequently, implemented in a phase I clinical trial for pharmacokinetic evaluation of the new cytotoxic agent.

Aged↗
PubMed1990

Chemical stability of suramin in commonly used infusion fluids.

The chemical stability of suramin in NaCl 0.9%, dextrose 5%, and lactated Ringer's injection was investigated. The admixtures were stored in glass infusion bottles at 4 degrees C in the dark, and at room temperature (22 degrees C) both protected from light and under normal room fluorescent light conditions in a day-night rhythm. The initial concentration of suramin was approximately 1 mg/mL. Samples withdrawn immediately after preparation and at four hours, one, two, three, five, and seven days were analyzed by HPLC with ultraviolet (UV) detection. Samples were also inspected for visual changes and tested for changes in pH. Accelerated stability studies in NaCl 0.9% injection were executed at 90 degrees C. The drug appeared to be stable under the chosen storage conditions with no visual changes or changes in pH. The accelerated experiments revealed that suramin degrades in NaCl 0.9% at 90 degrees C with a half-life of about 5.5 hours. It is concluded that suramin 1 mg/mL is stable in NaCl 0.9%, dextrose 5%, and lactated Ringer's injections when stored in glass infusion bottles at 4 degrees C in the dark and at 22 degrees C under normal room light conditions in a day-night rhythm or protected from light for at least seven days.

Chromatography, High Pressure Liquid↗
PubMed1989

Bio-analysis and preliminary pharmacokinetics of the experimental antitumour drug LL-D49194 alpha 1.

LL-D49194 alpha 1 is a recently discovered compound, produced by Streptomyces vinaceus-drappus. This micro-organism produces a number of antibiotics, all showing antibacterial and antitumour activity, of which LL-D49194 alpha 1 is one of the main compounds. The compounds' antitumour effectiveness has been proven in vitro and the drug is undergoing further tests. For the assay of the drug in plasma a high-performance liquid chromatographic (HPLC) system has been developed, preceded by a clean-up step. The drug is extracted from the biological matrix with ethyl acetate followed by direct HPLC analysis of the organic layer via an analytical RP8 column preceded by a guard column to retain endogenous plasma compounds. Detection of drug and metabolites was carried out by fluorescence with reference to a non-fluorescent internal standard detected by UV absorption. The detection limit was 1 ng ml-1 plasma (using 1 ml sample; signal-to-noise ratio, 3), i.e. 1 ng on column. The method has been utilized in a preliminary pharmacokinetic study in rat.

Aminoglycosides↗