Abstract
A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitation of exemestane (Exe) and its main metabolite 17-dihydroexemestane (DhExe) in human plasma. The analytes were extracted by protein precipitation with acetonitrile, containing stable 13C-labelled Exe ( 13C 3-Exe) as internal standard, and measured by LC-MS/MS. The best chromatographic separationof the analytes from the interferences was achieved by using a Phenyl column operating under isocratic regime conditions. The total chromatographic runtime was 5.0 min and the elution of Exe and DhExe occurred at 2.5 min and 2.9 min, respectively. Quantitation was performed by employing the positive electrospray ionization (ESI) technique and multiple reaction monitoring mode (MRM). The monitored precursor to product-ion transitions for Exe, DhExe and 13C 3-Exe internal standard were m/z 297.0 → 120.8, m/z 299.1 → 134.9 and m/z 300.0 → 123.2, respectively. The lower limit of quantitation (LLOQ) was 0.1 ng/ml for DhExe and 0.2 ng/ml for Exe. The method was linear up to 36-51 ng/ml with r 2 ≥ 0.998. The intra- and inter-assay precision were ≤7.7% and 5.1% for Exe and ≤8.1 and 4.9% for DhExe while deviations from nominal values were in the 1.5-13.2% and -9.0-5.8% ranges for Exe and DhExe, respectively. The analytical method resulted robust and suitable for pharmacokinetic monitoring of Exe and its main metabolite during adjuvant therapy in patients with breast cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 920-928 |
| Number of pages | 9 |
| Journal | Journal of Mass Spectrometry |
| Volume | 44 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2009 |
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Keywords
- 17-dihydroexemestane
- Electrospray ionization
- Exemestane
- Liquid chromatography
- Pharmacokinetics
- Tandem mass spectroscopy
ASJC Scopus subject areas
- Spectroscopy
Cite this
A liquid chromatography-tandemmass spectrometry method for the simultaneous determination of exemestane and its metabolite 17-dihydroexemestane in human plasma. / Corona, Giuseppe; Elia, Caterina; Casetta, Bruno; Diana, Crivellari; Rosalen, Sara; Bari, Mario; Toffoli, Giuseppe.
In: Journal of Mass Spectrometry, Vol. 44, No. 6, 06.2009, p. 920-928.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A liquid chromatography-tandemmass spectrometry method for the simultaneous determination of exemestane and its metabolite 17-dihydroexemestane in human plasma
AU - Corona, Giuseppe
AU - Elia, Caterina
AU - Casetta, Bruno
AU - Diana, Crivellari
AU - Rosalen, Sara
AU - Bari, Mario
AU - Toffoli, Giuseppe
PY - 2009/6
Y1 - 2009/6
N2 - A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitation of exemestane (Exe) and its main metabolite 17-dihydroexemestane (DhExe) in human plasma. The analytes were extracted by protein precipitation with acetonitrile, containing stable 13C-labelled Exe ( 13C 3-Exe) as internal standard, and measured by LC-MS/MS. The best chromatographic separationof the analytes from the interferences was achieved by using a Phenyl column operating under isocratic regime conditions. The total chromatographic runtime was 5.0 min and the elution of Exe and DhExe occurred at 2.5 min and 2.9 min, respectively. Quantitation was performed by employing the positive electrospray ionization (ESI) technique and multiple reaction monitoring mode (MRM). The monitored precursor to product-ion transitions for Exe, DhExe and 13C 3-Exe internal standard were m/z 297.0 → 120.8, m/z 299.1 → 134.9 and m/z 300.0 → 123.2, respectively. The lower limit of quantitation (LLOQ) was 0.1 ng/ml for DhExe and 0.2 ng/ml for Exe. The method was linear up to 36-51 ng/ml with r 2 ≥ 0.998. The intra- and inter-assay precision were ≤7.7% and 5.1% for Exe and ≤8.1 and 4.9% for DhExe while deviations from nominal values were in the 1.5-13.2% and -9.0-5.8% ranges for Exe and DhExe, respectively. The analytical method resulted robust and suitable for pharmacokinetic monitoring of Exe and its main metabolite during adjuvant therapy in patients with breast cancer.
AB - A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitation of exemestane (Exe) and its main metabolite 17-dihydroexemestane (DhExe) in human plasma. The analytes were extracted by protein precipitation with acetonitrile, containing stable 13C-labelled Exe ( 13C 3-Exe) as internal standard, and measured by LC-MS/MS. The best chromatographic separationof the analytes from the interferences was achieved by using a Phenyl column operating under isocratic regime conditions. The total chromatographic runtime was 5.0 min and the elution of Exe and DhExe occurred at 2.5 min and 2.9 min, respectively. Quantitation was performed by employing the positive electrospray ionization (ESI) technique and multiple reaction monitoring mode (MRM). The monitored precursor to product-ion transitions for Exe, DhExe and 13C 3-Exe internal standard were m/z 297.0 → 120.8, m/z 299.1 → 134.9 and m/z 300.0 → 123.2, respectively. The lower limit of quantitation (LLOQ) was 0.1 ng/ml for DhExe and 0.2 ng/ml for Exe. The method was linear up to 36-51 ng/ml with r 2 ≥ 0.998. The intra- and inter-assay precision were ≤7.7% and 5.1% for Exe and ≤8.1 and 4.9% for DhExe while deviations from nominal values were in the 1.5-13.2% and -9.0-5.8% ranges for Exe and DhExe, respectively. The analytical method resulted robust and suitable for pharmacokinetic monitoring of Exe and its main metabolite during adjuvant therapy in patients with breast cancer.
KW - 17-dihydroexemestane
KW - Electrospray ionization
KW - Exemestane
KW - Liquid chromatography
KW - Pharmacokinetics
KW - Tandem mass spectroscopy
UR - http://www.scopus.com/inward/record.url?scp=67649158224&partnerID=8YFLogxK
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U2 - 10.1002/jms.1566
DO - 10.1002/jms.1566
M3 - Article
VL - 44
SP - 920
EP - 928
JO - Biomedical Mass Spectrometry
JF - Biomedical Mass Spectrometry
SN - 1076-5174
IS - 6
ER -