Simultaneous quantification of ten cytotoxic drugs by a validated LC–ESI–MS/MS method

Abstract

A liquid chromatography separation with electrospray ionisation and tandem mass spectrometry detection method was developed for the simultaneous quantification of ten commonly handled cytotoxic drugs in a hospital pharmacy. These cytotoxic drugs are cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. The chromatographic separation was carried out by RPLC in less than 21 min, applying a gradient elution of water and acetonitrile in the presence of 0.1% formic acid. MS/MS was performed on a triple quadrupole in selected reaction monitoring mode. The analytical method was validated to determine the limit of quantification (LOQ) and quantitative performance: lowest LOQs were between 0.25 and 2 ng mL(-1) for the ten investigated cytotoxic drugs; trueness values (i.e. recovery) were between 85% and 110%, and relative standard deviations for both repeatability and intermediate precision were always inferior to 15%. The multi-compound method was successfully applied for the quality control of pharmaceutical formulations and for analyses of spiked samples on potentially contaminated surfaces.

Capillary Electrophoresis with Laser-induced Fluorescence Detection for Application in Intracellular Investigation of Anthracyclines and Multidrug Resistance Proteins

“…The LOD for DOX, determined by LC-ESI-MS/MS 33 (1 ng mL -1 ) is comparable with CE-LIF. However, the quantitation range of DOX determined by LC-ESI-MS/MS 33 (10 -100 ng mL -1 ) is narrow compared to that determined by LIF-CE.…”

“…The bulk of anthracylines determinations are done by either capillary electrophoretic 13,14,[20][21][22][23][24][25] or chromatographic 11,12,[29][30][31][32][33] techniques coupled with various detectors, including UV, LIF and mass spectrometry. Chromatography has several advantages, including superior sensitivity but requires large amounts of solvents, expensive columns and equipment, comparatively larger sample size and the extraction of analytes.…”

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

“…4,9,10 Most of the reported methods are based on the use of liquid chromatography (LC) coupled with UV spectrophotometry (UV) 11,12,13,14 or mass spectrometry (MS), when there was a need for high selectivity and/or sensitivity. [15][16][17][18][19][20][21][22]23,24,25,26,27,28,29,30,31,32,33,34 Limits of detection 51 In our opinion, ELSD is not recommended for analysing pemetrexed since this molecule is UV-active and ELSD is often less sensitive and selective than the commonly used UV detectors. A methodology including a PP step followed by LC-MS analysis was also developed for the determination of raltitrexed in human plasma with a limit of quantification (LOQ) of 2 ng mL −1 .…”

“…18,19,134,307,422 Vinca alcaloid extraction from plants was generally performed by ultrasound in acid media followed by LLE. 45,[398][399][400][401] CE methods are scarcely reported for the determination of vinca alkaloids.…”

Environmental Contaminations and Occupational Exposures Involved in Preparation of Chemotherapeutic Drugs

“…However, there are only several reports in the fields of occupational exposures to healthcare workers [Larson et al,2003;Sabatini et al,2005;Sottani et al,2007Sottani et al, , 2008Nussbaumer et al,2010].…”