Multianalyte determination of 24 cytostatics and metabolites by liquid chromatography-electrospray-tandem mass spectrometry and study of their stability and optimum storage conditions in aqueous solution
A multianalyte liquid chromatography-electrospray-tandem mass spectrometry (LC-ESI-MS/MS) method for determination of 19 cytostatics and 5 metabolites, from 6 different therapeutic families, has been developed, and the structures of the main characteristic fragment ions have been proposed. Instrumental limits of detection and quantification are in the range 0.1-10.3 and 1.0-34.3 ng mL−1, respectively. Moreover, the stability of the compounds in aqueous solution was investigated in order to establish the best conditions for preparation and storage of both calibration standards and water samples. Dimethylsulfoxide (DMSO) was selected as solvent for preparation of the stock solutions. At room temperature (25 ºC), 11 of the 24 target compounds were shown to be unstable in water (percentage of organic solvent 4%), with concentration losses greater than 20% in less than 24 h. At 4 ºC (typical storage temperature for water samples) all compounds, except MTIC and chlorambucil, were stable for 24 h, but the number of stable compounds decreased to 10 after 9 days. Freezing of the aqueous solutions improved considerably the stability of various compounds: after 3 months of storage at -20 ºC, 10 compounds, namely, 5-fluorouracil, carboplatin, gemcitabine, temozolomide, vincristine, vinorelbine, ifosfamide, cyclophosphamide, etoposide, and capecitabine, remained stable (in contrast to only carboplatin and capecitabine at 4 ºC). The addition of acid improved the stability of methotrexate and its metabolite hydroxymethotrexate but not that of the rest of compounds. The addition of organic solvent (50% methanol or DMSO) prevented the degradation at 4 ºC of the otherwise unstable compounds oxaliplatin, methotrexate, erlotinib, doxorubicin, tamoxifen, and paclitaxel. To the authors' knowledge, five of the analytes investigated have never been searched for in the aquatic environment (imatinib, 6α-hydroxypaclitaxel, endoxifen, (Z)4- Hydroxytamoxifen, and temozolomide), and for many of them the stability data provided, and even the analytical LC-MS/MS conditions, are the first ever published.
| Main Authors: | , , , |
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| Format: | artículo biblioteca |
| Language: | English |
| Published: |
Elsevier
2013-11-15
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| Subjects: | Cytostatics, Water samples, Stability, Electrospray, Fragmentation, Liquid chromatography-mass spectrometry, |
| Online Access: | http://hdl.handle.net/10261/76588 |
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| Summary: | A multianalyte liquid chromatography-electrospray-tandem mass
spectrometry (LC-ESI-MS/MS) method for determination of 19 cytostatics
and 5 metabolites, from 6 different therapeutic families, has been
developed, and the structures of the main characteristic fragment ions
have been proposed. Instrumental limits of detection and quantification
are in the range 0.1-10.3 and 1.0-34.3 ng mL−1, respectively. Moreover,
the stability of the compounds in aqueous solution was investigated in
order to establish the best conditions for preparation and storage of
both calibration standards and water samples. Dimethylsulfoxide (DMSO)
was selected as solvent for preparation of the stock solutions. At room
temperature (25 ºC), 11 of the 24 target compounds were shown to be
unstable in water (percentage of organic solvent 4%), with concentration
losses greater than 20% in less than 24 h. At 4 ºC (typical storage
temperature for water samples) all compounds, except MTIC and
chlorambucil, were stable for 24 h, but the number of stable compounds
decreased to 10 after 9 days. Freezing of the aqueous solutions improved
considerably the stability of various compounds: after 3 months of
storage at -20 ºC, 10 compounds, namely, 5-fluorouracil, carboplatin,
gemcitabine, temozolomide, vincristine, vinorelbine, ifosfamide,
cyclophosphamide, etoposide, and capecitabine, remained stable (in
contrast to only carboplatin and capecitabine at 4 ºC). The addition of
acid improved the stability of methotrexate and its metabolite hydroxymethotrexate
but not that of the rest of compounds. The addition of
organic solvent (50% methanol or DMSO) prevented the degradation at 4 ºC
of the otherwise unstable compounds oxaliplatin, methotrexate, erlotinib,
doxorubicin, tamoxifen, and paclitaxel. To the authors' knowledge, five
of the analytes investigated have never been searched for in the aquatic
environment (imatinib, 6α-hydroxypaclitaxel, endoxifen, (Z)4-
Hydroxytamoxifen, and temozolomide), and for many of them the stability
data provided, and even the analytical LC-MS/MS conditions, are the first
ever published. |
|---|