Quantification of trabectedin in human plasma: Validation of a high-performance liquid chromatography-mass spectrometry method and its application in a clinical pharmacokinetic study

Monique Zangarini, Laura Ceriani, Federica Sala, Elena Marangon, Renzo Bagnati, Maurizio D'Incalci, Federica Grosso, Massimo Zucchetti

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9 Citations (Scopus)

Abstract

A rapid, sensitive and specific HPLC-MS/MS method was developed and validated for the quantification of trabectedin in human plasma after using deuterated trabectedin as Internal Standard (IS). After the addition of ammonium sulphate, the analyte was extracted from human plasma with acidified methanol (0.1M HCl). Chromatographic separation was done on an Accucore XL C18 column (4μm; 50mm×2.1mm) using a Mobile Phase (MP) consisting of CH3COONH4 10mM, pH 6.8 (MP A) and CH3OH (MP B). The mass spectrometer worked with electrospray ionization in positive ion mode and Selected Reaction Monitoring (SRM), using target ions at [M-H2O+H]+ m/z 744.4 for trabectedin and [M-H2O+H]+ m/z 747.5 for the IS. The standard curve was linear (R2≥0.9955) over the concentration range 0.025-1.0ng/ml and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy determined on three quality control samples (0.04, 0.08 and 0.80ng/ml) were 81% and the lower limit of quantification 0.025ng/ml. The method was successfully applied to study trabectedin pharmacokinetics in a patient with a liposarcoma who received 1.3mg/m2 as a 24h continuous i.v. infusion.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume95
DOIs
Publication statusPublished - 2014

Fingerprint

trabectedin
Plasma (human)
Pharmacokinetics
High performance liquid chromatography
Mass spectrometry
Mass Spectrometry
High Pressure Liquid Chromatography
Ions
Liposarcoma
Electrospray ionization
Ammonium Sulfate
Mass spectrometers
Quality Control
Quality control
Methanol
Positive ions
Clinical Studies
Monitoring

Keywords

  • HPLC-MS/MS
  • Human plasma
  • Liposarcoma
  • Pharmacokinetics
  • Trabectedin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Spectroscopy
  • Clinical Biochemistry
  • Medicine(all)

Cite this

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title = "Quantification of trabectedin in human plasma: Validation of a high-performance liquid chromatography-mass spectrometry method and its application in a clinical pharmacokinetic study",
abstract = "A rapid, sensitive and specific HPLC-MS/MS method was developed and validated for the quantification of trabectedin in human plasma after using deuterated trabectedin as Internal Standard (IS). After the addition of ammonium sulphate, the analyte was extracted from human plasma with acidified methanol (0.1M HCl). Chromatographic separation was done on an Accucore XL C18 column (4μm; 50mm×2.1mm) using a Mobile Phase (MP) consisting of CH3COONH4 10mM, pH 6.8 (MP A) and CH3OH (MP B). The mass spectrometer worked with electrospray ionization in positive ion mode and Selected Reaction Monitoring (SRM), using target ions at [M-H2O+H]+ m/z 744.4 for trabectedin and [M-H2O+H]+ m/z 747.5 for the IS. The standard curve was linear (R2≥0.9955) over the concentration range 0.025-1.0ng/ml and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy determined on three quality control samples (0.04, 0.08 and 0.80ng/ml) were 81{\%} and the lower limit of quantification 0.025ng/ml. The method was successfully applied to study trabectedin pharmacokinetics in a patient with a liposarcoma who received 1.3mg/m2 as a 24h continuous i.v. infusion.",
keywords = "HPLC-MS/MS, Human plasma, Liposarcoma, Pharmacokinetics, Trabectedin",
author = "Monique Zangarini and Laura Ceriani and Federica Sala and Elena Marangon and Renzo Bagnati and Maurizio D'Incalci and Federica Grosso and Massimo Zucchetti",
year = "2014",
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volume = "95",
pages = "107--112",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
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publisher = "Elsevier",

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T1 - Quantification of trabectedin in human plasma

T2 - Validation of a high-performance liquid chromatography-mass spectrometry method and its application in a clinical pharmacokinetic study

AU - Zangarini, Monique

AU - Ceriani, Laura

AU - Sala, Federica

AU - Marangon, Elena

AU - Bagnati, Renzo

AU - D'Incalci, Maurizio

AU - Grosso, Federica

AU - Zucchetti, Massimo

PY - 2014

Y1 - 2014

N2 - A rapid, sensitive and specific HPLC-MS/MS method was developed and validated for the quantification of trabectedin in human plasma after using deuterated trabectedin as Internal Standard (IS). After the addition of ammonium sulphate, the analyte was extracted from human plasma with acidified methanol (0.1M HCl). Chromatographic separation was done on an Accucore XL C18 column (4μm; 50mm×2.1mm) using a Mobile Phase (MP) consisting of CH3COONH4 10mM, pH 6.8 (MP A) and CH3OH (MP B). The mass spectrometer worked with electrospray ionization in positive ion mode and Selected Reaction Monitoring (SRM), using target ions at [M-H2O+H]+ m/z 744.4 for trabectedin and [M-H2O+H]+ m/z 747.5 for the IS. The standard curve was linear (R2≥0.9955) over the concentration range 0.025-1.0ng/ml and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy determined on three quality control samples (0.04, 0.08 and 0.80ng/ml) were 81% and the lower limit of quantification 0.025ng/ml. The method was successfully applied to study trabectedin pharmacokinetics in a patient with a liposarcoma who received 1.3mg/m2 as a 24h continuous i.v. infusion.

AB - A rapid, sensitive and specific HPLC-MS/MS method was developed and validated for the quantification of trabectedin in human plasma after using deuterated trabectedin as Internal Standard (IS). After the addition of ammonium sulphate, the analyte was extracted from human plasma with acidified methanol (0.1M HCl). Chromatographic separation was done on an Accucore XL C18 column (4μm; 50mm×2.1mm) using a Mobile Phase (MP) consisting of CH3COONH4 10mM, pH 6.8 (MP A) and CH3OH (MP B). The mass spectrometer worked with electrospray ionization in positive ion mode and Selected Reaction Monitoring (SRM), using target ions at [M-H2O+H]+ m/z 744.4 for trabectedin and [M-H2O+H]+ m/z 747.5 for the IS. The standard curve was linear (R2≥0.9955) over the concentration range 0.025-1.0ng/ml and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy determined on three quality control samples (0.04, 0.08 and 0.80ng/ml) were 81% and the lower limit of quantification 0.025ng/ml. The method was successfully applied to study trabectedin pharmacokinetics in a patient with a liposarcoma who received 1.3mg/m2 as a 24h continuous i.v. infusion.

KW - HPLC-MS/MS

KW - Human plasma

KW - Liposarcoma

KW - Pharmacokinetics

KW - Trabectedin

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