Detection of doxorubicin and metabolites in cell extracts and in single cells by capillary electrophoresis with laser-induced fluorescence detection

Anderson, Adrian B.; Gergen, Jamie; Arriaga, Edgar A.

doi:10.1016/s1570-0232(01)00633-x

Cited by 76 publications

(62 citation statements)

References 33 publications

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“…Four 1.2 mL samples were removed for cellular extraction (following an adaption of the method of Anderson et al (2002)). The medium from the first spin was also collected, and 50 mL processed using the method of Zhou and Chowbay (2002).…”

Section: Estimation Of Equilibrium Partition Coefficient In Cell Linesmentioning

confidence: 99%

A novel system for evaluation of drug mixtures for potential efficacy in treating multidrug resistant cancers

Tatosian

Shuler

2009

Biotech & Bioengineering

128

107

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Multidrug resistant (MDR) cancer is difficult to treat. Chemicals that are effective MDR modulators have never exited clinical trials as FDA approved products due to side effects. It has been hypothesized that using a combination of chemotherapeutics with a mixture of MDR modulators (each with different side effects) may lead to useful treatment strategies. Because the experimental space for combination treatments can be large, this space may be impracticable to explore using animal studies. Here we describe an in vitro system based on microfabrication and cell culture that can potentially be used to explore large experimental spaces efficiently. The Microscale Cell Culture Analog (microCCA) concept mimics the body's response using interconnected compartments that represent various tissues or organs. A microCCA is based on the structure of an appropriate physiologically based pharmacokinetic (PBPK) model and emulates the body's dynamic response to exposure to various drugs and chemicals. For this problem we have chosen a microCCA with living cells representing the liver (HepG2/C3A), bone marrow (MEG-01), uterine cancer (MES-SA), and a MDR variant of uterine cancer (MES-SA/DX-5). In proof of concept experiments we found in 24 h "acute" exposures and 72 h treatments that the microCCA system predicts combining the chemotherapeutic, doxorubicin, with cyclosporine and nicardipine, as MDR modulators will have greater efficacy than using doxorubicin by itself or with either modulator alone. This combined strategy is selective in inhibiting MES-SA/DX-5 cell proliferation and may prove to be advantageous in vivo by specifically targeting MDR cancer with acceptable side-effects. This cell specific synergy was not observed in traditional 96-well plate assays. By combining the microCCA with a PBPK model, appropriate drug doses and area under the curve exposure for in vivo trials can be extrapolated directly from the results obtained with this device. This device and approach should be useful in screening potential drug/modulator combinations to determine candidate treatments for MDR cancer. Indeed this approach may be useful for in vitro evaluation of human response to a wide range of exposures to mixtures of chemicals or drugs.

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Section: Estimation Of Equilibrium Partition Coefficient In Cell Linesmentioning

confidence: 99%

A novel system for evaluation of drug mixtures for potential efficacy in treating multidrug resistant cancers

Tatosian

Shuler

2009

Biotech & Bioengineering

128

107

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“…Optical sensing techniques are mainly used for bulk measurements [1,2] but they are less suitable for measurements at single cells or small cell clusters. This is because of rapid homogenization of the transported species due to efficient mass transport at a microscopic scale, resulting in very small local changes in analyte concentrations.…”

Section: Introductionmentioning

confidence: 99%

MEMS Device to Monitor Biological Oxygen Uptake at Arrays of Single Cells and Small Cell Clusters

et al. 2008

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Oxygen uptake by a cell is indicative of metabolic processes which are modulated by extracellular stimuli and is characteristic of a cells physiological status. In this work, a MEMS platform with an array of microsensors to monitor these processes at cell constructs is being developed. An array of Pt microring electrodes has been fabricated to quantitatively assess oxygen uptake by normal and pharmacologically manipulated BAC1.2F5 macrophage cells positioned at cell attachment sites inside the microrings. An amperometric pulsing protocol was implemented to reduce interference with cellular metabolism caused by depletion of oxygen during the measurement. We were able to detect changes as small as 1% in oxygen concentration in the vicinity of single cells and small cell clusters. Thus, the approach can be used for sensitive indication of oxygen uptake by cell(s) and its modulation by environmental factors such as pharmacological agents, and interaction with adjacent cells. Moreover, parallel experiments at different cell attachment sites are made feasible by the sensor array. This can provide multiple data sets for biostatistics in the same amount of time that is required to get a single data set.

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“…339 LC-ELSD was also applied for the analysis of daunorubicin and its degradation products for a stability study of injectable solution of anthracycline (0.25 mg mL −1 was the lowest concentration of standard solutions tested), but the interest of ELSD for anthracyclines is not obvious since these molecules can be easily detected by UV, FD and MS. 340 As already mentioned, CE was another separation technique widely used for the determination of anthracyclines. LIF detection [341][342][343][344][345][346][347][348][349] is usually preferred to UV detection 350 to improve sensitivity. However, the poor UV sensitivity observed in CE (due to the narrow optical path of the capillaries) can be compensated for by a sweeping preconcentration step and an electrokinetic injection.…”

Section: Intercalating Agentsmentioning

confidence: 99%

Antineoplastic drugs and their analysis: a state of the art review

Guichard

Guillarme

Bonnabry

et al. 2017

Analyst

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The number of patients suffering from cancer is constantly increasing and, consequently, the number of different chemotherapy treatments administered is increasing. Given the high reactivity and toxicity of antineoplastic drugs, analytical methods are required in all pharmaceutical fields, from drug development to their elimination in wastewater; including formulation quality control, environment and human exposure and therapeutic drug monitoring. The aim of this paper is to provide an overview of the analytical methods available for the determination of antineoplastic drugs in different matrices such as pharmaceutical formulations, biological and environmental samples. The applicability and performance of the reported methods will be critically discussed, with focus on the most commonly used antineoplastic drugs. Only conventional compounds and small molecules for targeted therapy will be considered in the present review.

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Detection of doxorubicin and metabolites in cell extracts and in single cells by capillary electrophoresis with laser-induced fluorescence detection

Cited by 76 publications

References 33 publications

A novel system for evaluation of drug mixtures for potential efficacy in treating multidrug resistant cancers

A novel system for evaluation of drug mixtures for potential efficacy in treating multidrug resistant cancers

MEMS Device to Monitor Biological Oxygen Uptake at Arrays of Single Cells and Small Cell Clusters

Antineoplastic drugs and their analysis: a state of the art review

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