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

Abstract

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.

HPLC–UV method for temozolomide determination in complex biological matrices: Application for in vitro, ex vivo and in vivo studies

“…This result was similar to the recovery reported by Kim et al, who found a recovery for TMZ in human plasma of ~47–50% to a concentration range of 0.1–20 mg/mL (Kim et al, ). Another previous study obtained a recovery between 40.7 and 55.5% for a 5.000 μg/mL concentration of TMZ in plasma and a recovery about 60% for 125–12.500 ng/g in brain (Goldwirt et al, ). In this context, the development of a method able to quantify low levels of TMZ and to recover high drug contents from biological samples is a key consideration in pharmaceutical development, taking into account that the previous described methodologies for TMZ quantification in biological samples employ a complex extraction method or result in low drug recovery.…”

“…Nevertheless, during pharmaceutical development, it is essential to use an adequate methodology for drug determination in analytical or bioanalytical assays, with an accurate quantification of the compounds of interest (Baptista, Oliveira, & Ferreira, ; Yazbi, Hassan, Khamis, Ragab, & Hamdy, ). Some methods, including high‐pressure liquid chromatography with ultraviolet (HPLC–UV) detection (Shen et al, ; Gilant, Kaza, Szlagowska, Serafin‐byczak, & Rudzki, ; Jain, Athawale, Bajaj, & Shrikhande, ), ultra‐performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) (Goldwirt, Zahr, Farinotti, & Fernandez, ) and liquid chromatography tandem mass spectrometry (LC–MS/MS) (Diez et al, ), have been reported for TMZ analysis.…”

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

“…Few methods based on LC-UV [256][257][258][259][260][261] and LC-MS [262][263][264][265][266] were reported for the analysis of triazene compounds and procardazine in biological matrices. An LOQ of 0.5 ng mL −1 was achieved for the analysis of dacarbazine 266 and procarbazine 265 in plasma samples by LC-MS. Lower sensitivity (LOQ of 50 ng mL −1 ) was reached with LC-MS for the temozolomide assay in plasma.…”

“…An LOQ of 0.5 ng mL −1 was achieved for the analysis of dacarbazine 266 and procarbazine 265 in plasma samples by LC-MS. Lower sensitivity (LOQ of 50 ng mL −1 ) was reached with LC-MS for the temozolomide assay in plasma. 264 A micellar electrokinetic chromatography (MEKC) method has also been reported for the determination of temozolomide and its degradation products in water and serum. 267 The choice of the MEKC method was based on: (i) the absence of charge on temozolomide in neutral and acidic conditions; and (ii) its low stability in solution.…”

Preclinical impact of bevacizumab on brain and tumor distribution of irinotecan and temozolomide

“…Whole brains were collected, rinsed with 0.9 % sodium chloride and directly frozen at -20°C in polyethylene tubes. Temozolomide levels in mice plasma and brains were measured using their respective assay procedures as previously published [24].…”