A liquid chromatography-tandemmass spectrometry method for the simultaneous determination of exemestane and its metabolite 17-dihydroexemestane in human plasma

Giuseppe Corona, Caterina Elia, Bruno Casetta, Crivellari Diana, Sara Rosalen, Mario Bari, Giuseppe Toffoli

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish
Pages (from-to)920-928
Number of pages9
JournalJournal of Mass Spectrometry
Volume44
Issue number6
DOIs
Publication statusPublished - Jun 2009

Fingerprint

exemestane
Plasma (human)
metabolites
Liquid chromatography
liquid chromatography
Metabolites
Liquid Chromatography
Spectrometry
Assays
Spectrum Analysis
Electrospray ionization
elution
Pharmacokinetics
Monitoring
Acetonitrile
breast
spectroscopy
acetonitrile
Mass spectrometry
therapy

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 journalArticle

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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.",
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AU - Corona, Giuseppe

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AU - Rosalen, Sara

AU - Bari, Mario

AU - Toffoli, Giuseppe

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