Determination of the glucuronide metabolite of ON 013100, a benzylstyrylsulfone antineoplastic drug, in colon cancer cells using LC/MS/MS (original) (raw)
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Cancer research, 1987
The biological half-lives and decay rate constants under the conditions of a human brain tumor clonogenic cell assay were determined for six clinically used anticancer agents. The agents studied were: 1,3-bis(2-chloroethyl)-1-nitrosourea; 3-(2-chloroethyl-3-nitrosoureido-2-deoxy-D-glucopyranose; cis-diaminedichloroplatinum(II); 2,5-diaziridinyl-3,6-bis-(carboethoxyamino)-1,4-benzoquinone; 4-demethylepipodophylotoxin-D-thylidene glucoside; and 9-hydroxy-2-N-methylellipticine. In vitro decay of all six drugs was found to be according to first order kinetics. The half-lives of two drugs, namely, 1,3-bis(2-chloroethyl-1-nitrosourea and 3-(2-chloroethyl-3-nitrosoureido-2-deoxy-D-glucopyranose under the human tumor clonogenic cell assay (HTCA) conditions were found to be similar to their terminal in vivo half-lives in humans. For the other drugs, however, there was a very large difference between their in vitro and in vivo pharmacokinetics. In the case of 2,5-diaziridinyl-3,6-bis(carboeth...
Cancer research, 1969
Human and animal leukemias, varying widely in responsive ness to 6-mercaptopurine, were examined to seek determinants of drug sensitivity. Drug-responsive rodent leukemias showed a comparatively high capacity for in vitro conversion of 6-mer captopurine into nondiffusible cellular metabolites, predomi nantly drug nucleotides. A similar study of human leukemia cells indicated that the in vitro capacity for 6-mercaptopurine anabolism can also be a useful predictive measure of drug responsiveness in man.
Analysis of Antineoplastic Drugs: Clinical Pharmacology and Therapeutic Study
The current study depicts that it is observed the even the slight presence of easily oxidizable substance like thio-urea, ascorbic acid, hydrazine; alcohols etc. interfere in the estimation. In such case higher recovery is obtained because the compound reacts with the reagent. Therefore, the presence of such substances was avoided. Excipients like starch, calcium carbonate, sodium carbonate, cellulose, magnesium tri-silicate, tri-calcium phosphate and gum acacia if present in the pharmaceutical preparations do not interfere in the estimation. Background: Antineoplastic agents are a group of specialized drugs used primarily to treat cancer (the term "neoplastic" refers to cancer cells). The first antineoplastic agents used in the 1940s, were made from either synthetic chemicals or natural plants. Antineoplastic agents are classified by origin and by how they work to destroy cancer cells. Antineoplastic agents can be administered to patients alone or in combination with other antineoplastic drugs. They can also be given before, during or after a patient receives surgery radiation therapy. Antineoplastic agents travel the body and destroy cancer cells.Side effects are expected to occur when treated with these agents, and can include nausea, mouth sores, hair loss, and lowering of the blood counts. Many of the side effects associated with antineoplastic agents occur because chemotherapy treatment destroys the body's normal cells in addition to cancerous cells. Materials and Methods: An aliquot containing 5mg of the sample was taken in a l00mL stoppered conical flask and 5mL of 0.02NNCS reagent, prepared in hydrochloric acid and 5mL of 4N hydrochloric acid was added to it. The reaction mixture was shaken thoroughly and allowed to react for 15minutes at room temperature (25-300C). After the reaction is over 5mL of 5% potassium iodide was added to it. Contents were shaken thoroughly and allowed to react for a minute. The unconsumed NCS was determined iodometrically. A blank experiment was also run under identical conditions using all the reagents except the sample. Results: Methotrexate is a complex compound having six membered heterocyclic ring attached to substituted benzene ring which has got a side chain at para position attached to-NH2 group. The most probable reaction may be chlorination of the benzene ring at ortho position to substituted nitrogen atom. On this basis following reaction product may be postulated.Cytarabine is a derived pyrimidine base nucleus. One of the nitrogen is substituted five membered heterocyclic ring which contain a side chain having a primary hydroxy group. Etoposide is another complex molecule containing two benzene ring along with two five membered rings. One of the ring is highly substituted at ortho and meta position. The other benzene ring has got two five membered substituted cyclic rings. It has also got a glucopyranose ring attached through live membered cyclic ring. It becomes difficult to predict the reaction of this compound with NCS. The central benzene ring has got two active positions at para positions. Therefore chlorination may happen on these available positions. Doxorubicin hydrochloride has got four cyclic rings of which the main molecule is anthraquinone derivative. Conclusion: The current study depicts that it is observed the even the slight presence of easily oxidizable substance like thio-urea, ascorbic acid, hydrazine; alcohols etc. interfere in the estimation. In such case higher recovery is obtained because the compound reacts with the reagent. Therefore, the presence of such substances was avoided. Excipients like starch, calcium carbonate, sodium carbonate, cellulose, magnesium tri-silicate, tri-calcium phosphate and gum acacia if present in the pharmaceutical preparations do not interfere in the estimation.
Analysis of anticancer drugs: A review
Talanta, 2011
In the last decades, the number of patients receiving chemotherapy has considerably increased. Given the toxicity of cytotoxic agents to humans (not only for patients but also for healthcare professionals), the development of reliable analytical methods to analyse these compounds became necessary. From the discovery of new substances to patient administration, all pharmaceutical fields are concerned with the analysis of cytotoxic drugs. In this review, the use of methods to analyse cytotoxic agents in various matrices, such as pharmaceutical formulations and biological and environmental samples, is discussed. Thus, an overview of reported analytical methods for the determination of the most commonly used anticancer drugs is given.
A Cell Fractionation Approach for the Quantitative Analysis of Subcellular Drug Disposition
Pharmaceutical Research, 2004
The purpose of this work was to develop and validate a method that can be used to quantify drugs associated with intracellular compartments. Methods. The human leukemic cell line U-937 was used to evaluate the distribution of model compounds with known and different subcellular distribution profiles. Lysotracker Red is a lysosomal vital stain and doxorubicin is an anticancer agent with a strong propensity for nuclear accumulation in U-937 cells. After incubation with compounds, cells were separated into fractions containing nuclei, cytosol, and cytoplasmic organelles (lysosomes, mitochondria, Golgi apparatus). Compounds contained within isolated fractions were subsequently extracted and analyzed by high-performance liquid chromatography. Diffusion of compounds from isolated organelles was also investigated. Results. Using this approach we have shown that the model compounds Lysotracker Red and doxorubicin preferentially accumulated within lysosomes and nuclei, respectively. We have reproducibly determined concentrations of these compounds in each of the cellular fractions. We have also shown that diffusion of these compounds from isolated cellular compartments was minimal during the time required to complete the experimental procedure. Conclusions. The analytical approach described in this manuscript yielded reproducible quantitative data regarding the intracellular distribution of model compounds in U-937 cells. With the aid of a relatively sensitive analytical assay, this technique should be useful for most drugs that have a specific concentrative mechanism for organelle accumulation similar to Dox and LTR.
Modern Approaches to Testing Drug Sensitivity of Patients’ Tumors (Review)
Sovremennye tehnologii v medicine, 2020
Drug therapy is still one of the basic techniques used to treat cancers of different etiology. However, tumor resistance to drugs is a pressing problem limiting drug treatment efficacy. It is obvious for both modern fundamental and clinical oncology that there is the need for an individual approach to treating cancer taking into account the biological properties of a tumor when prescribing chemo-and targeted therapy. One of the promising strategies is to increase the antitumor therapy efficacy by developing predictive tests, which enable to evaluate the sensitivity of a particular tumor to a specific drug or a drug combination before the treatment initiation and, thus, make individual therapy selection possible. The present review considers the main approaches to drug sensitivity assessment of patients' tumors: molecular genetic profiling of tumor cells, and direct efficiency testing of the drugs on tumor cells isolated from surgical or biopsy material. There were analyzed the key directions in research and clinical studies such as: the search for predictive molecular markers, the development of methods to maintain tumor cells or tissue sections viable, i.e. in a condition maximum close to their physiological state, the development of high throughput systems to assess therapy efficiency. Special attention was given to a patient-centered approach to drug therapy in colorectal cancer.
Journal of Natural Products, 1996
The development of simultaneous resistance to structurally unrelated drugs in cancer cells is a major obstacle to effective cancer chemotherapy. This multidrug-resistance (MDR) phenomenon is largely attributed to overexpression of a 170 kD glycoprotein, which serves as a transmembrane efflux pump in extruding a variety of natural anticancer drugs such as vinblastine, doxorubicin, and taxol from cancer cells. It is desirable, therefore, to discover compounds that can block the efflux mechanism and thus reverse drug resistance. The bicinchoninic acid protein assay has been adapted for use in a microtiter plate, into an easy, indirect method for screening MDR efflux blockers in plant extracts. This spectrophotometric assay is used t o determine the enhancement of adriamycin cytotoxicity against resistant cancer cells by plant extracts or pure compounds indirectly. We have shown that the optical density measured (amount of cellular protein present) correlates with the number of viable cells and that fluorescence of Adriamycin associated with the cell correlates with the concentrations of Adriamycin added to the media. In addition, the relative efficacy of MDR reversal by various alkaloids has been determined.