Determination of temozolomide in serum and brain tumor with micellar electrokinetic capillary chromatography

Andrási, Melinda; Törzsök, Brigitta; Klekner, Álmos; Gáspár, Attila

doi:10.1016/j.jchromb.2011.06.005

Cited by 15 publications

(7 citation statements)

References 23 publications

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“…A TMZ half-life of only 15 min in in vitro serum [13] and 33 min and 28 min in water at pH = 7.9 [14] was reported. MTIC half-lives of 1.9 h in human plasma in vivo [15,16], 25 min in human plasma in vitro [13,15], and 13 min in water pH = 7.9 [14] were determined. AIC is stable in human plasma [15] and in water at pH = 7.9 [14], at room temperature.…”

Section: Here Schemementioning

confidence: 99%

“…Considering that TMZ is a prodrug and that its degradation products in aqueous solution are responsible for its pharmacological activity, a few methods have been described for the analysis of TMZ and its metabolites in aqueous media, such as micellar electrokinetic capillary electrophoresis (MEKC) [14,16] and reverse-phase high performance liquid chromatography (HPLC) with UV [13,15,17] or MS/MS detection [18], was reported. However, an electrochemical investigation of the of TMZ chemical degradation processes in aqueous medium has not been carried out.…”

Section: Here Schemementioning

confidence: 99%

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Temozolomide chemical degradation to 5-aminoimidazole-4-carboxamide – Electrochemical study

Lopes

Oliveira

Oliveira-Brett

2013

Journal of Electroanalytical Chemistry

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The evaluation of the chemical degradation of temozolomide (TMZ), a potential anticancer drug, to its major metabolite 5-aminoimidazole-4-carboxamide (AIC), in aqueous solution with different pH values, was investigated at a glassy carbon electrode using cyclic and differential pulse voltammetry, and UV-Vis spectrophotometry. TMZ was incubated in aqueous solution, for different periods of time, and the changes in TMZ electrochemistry behaviour detected. The TMZ reduction is a pH-dependent irreversible process on the tetrazinone ring causing its irreversible breakdown. TMZ oxidation is a pH-dependent irreversible process that occurs in two consecutive charge transfer reactions. TMZ chemical degradation was electrochemically detected by the increase of the TMZ anodic peak current and the disappearance of the TMZ cathodic peak. The rate of chemical degradation increases with increasing pH and the mechanism corresponds to TMZ chemical degradation to AIC. The electrochemical behaviour of AIC over a wide pH range, was also investigated using cyclic, differential pulse and square wave voltammetry, AIC oxidation is an irreversible, diffusion-controlled process, pH-dependent up to a pH close to the pK a , and occurs in two consecutive charge transfer reactions, with the formation of two reversible redox products. A mechanism for AIC oxidation is proposed.

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Section: Here Schemementioning

confidence: 99%

Section: Here Schemementioning

confidence: 99%

Temozolomide chemical degradation to 5-aminoimidazole-4-carboxamide – Electrochemical study

Lopes

Oliveira

Oliveira-Brett

2013

Journal of Electroanalytical Chemistry

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“…Several plasma quantification methods on were developed using high‐performance liquid chromatography (HPLC) with ultra‐violet detection (Shen et al ., ; Kim et al ., ; Patel et al ., ) or liquid chromatography tandem mass spectrometry (LC‐MS/MS; Diez et al ., ) following different pre‐treatment liquid–liquid extraction (Kim et al ., ; Patel et al ., ) or solid‐phase extraction (Shen et al ., ). Only a few quantification methods in whole brain were described using HPLC with ultra‐violet detection or micellar electrokinetic capillary chromatography with photodiode‐array detection (Reyderman et al ., ; Andrasi et al ., ). The LLOQ of these methods (100 and 96 ng/mL for Reyderman and Andrasi study, respectively) may be not compatible with mouse brain and plasma pharmacokinetic studies.…”

Section: Introductionmentioning

confidence: 97%

Development of a new UPLC‐MSMS method for the determination of temozolomide in mice: application to plasma pharmacokinetics and brain distribution study

Goldwirt

Zahr

Farinotti

et al. 2013

Biomedical Chromatography

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A sensitive and accurate liquid chromatography method with mass spectrometry detection was developed and validated for the quantification of temozolomide in mouse plasma and brain. Theophyllin was used as the internal standard. A single-step protein precipitation was used for plasma and brain sample preparation. The method was validated with respect to selectivity, extraction recovery, linearity, intra- and inter-day precision and accuracy, limit of quantification and stability. The method has a limit of quantification of 50 ng/mL for temozolomide in plasma and 125 ng/g in brain. This method was used successfully to perform brain and plasma pharmacokinetic studies of temozolomide in mice after intraperitoneal administration.

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“…Nonetheless, its efficacy is limited due to its poor stability in the slightly alkaline conditions found in human plasma, [6]. TMZ is rapidly converted to MTIC and as a result has a short half-life of 1.8 h, so the concentration of TMZ both in serum and tumor sites drops to suboptimal levels very rapidly [20]. Moreover, the active metabolite MTIC, has a very poor BBB penetration and limited cellular absorption [21].…”

Section: Temozolomidementioning

confidence: 99%

Development of a validated LC-MS/MS method for the in vitro and in vivo quantitation of sunitinib in glioblastoma cells and cancer patients

Chatziathanasiadou

Stylos

Giannopoulou

et al. 2019

Journal of Pharmaceutical and Biomedical Analysis

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Temozolomide (TEMODAL™) (TMZ) is an antineoplastic agent that is primarily used for the treatment of glioblastoma and anaplastic gliomas, two aggressive forms of brain cancer. Due to the poor prognosis of brain tumour patients, there is an increasing body of research into improving the stability and delivery of TMZ past the blood brain barrier using carrier molecules. These require accurate determination of TMZ levels for biodistribution and pharmacokinetic evaluation. Unfortunately, current methodologies for the determination of TMZ in human plasma suffer from low reproducibility, recovery, sensitivity or cost ineffective procedures associated with extensive sample cleaning. To surpass these disadvantages, we developed two bioanalytical methods with high sensitivity and excellent recovery for the determination of TMZ in human plasma at minimum cost. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used and both methods were validated under US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) guidelines. The two methods had minor differences in the sample pre-treatment and each method was developed and applied in separate laboratories. Theophylline was selected as internal standard (IS). Calibration curves were linear over the range of 10-500 ng/mL with extraction recovery ranging from 77.3-97.3% while all validation parameters met the acceptance criteria and proved the methods' reliability. The validated methods were successfully applied to plasma samples donated from cancer patient following treatment with temozolomide.

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Determination of temozolomide in serum and brain tumor with micellar electrokinetic capillary chromatography

Cited by 15 publications

References 23 publications

Temozolomide chemical degradation to 5-aminoimidazole-4-carboxamide – Electrochemical study

Temozolomide chemical degradation to 5-aminoimidazole-4-carboxamide – Electrochemical study

Development of a new UPLC‐MSMS method for the determination of temozolomide in mice: application to plasma pharmacokinetics and brain distribution study

Development of a validated LC-MS/MS method for the in vitro and in vivo quantitation of sunitinib in glioblastoma cells and cancer patients

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