TY - JOUR
T1 - Novel method for fast trabectedin quantification using hydrophilic interaction liquid chromatography and tandem mass spectrometry for human pharmacokinetic studies
AU - Di Gregorio, Emanuela
AU - Miolo, Gianmaria
AU - Steffan, Agostino
AU - Corona, Giuseppe
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6/5
Y1 - 2020/6/5
N2 - Few time-consuming bioanalytical methods are currently available for trabectedin quantification in clinical investigations. Here we present a novel, fast and sensitive method for trabectedin determination in human plasma based on hydrophilic interaction liquid chromatography and tandem mass spectrometry (HILIC-MS/MS). Plasma samples are treated with acetonitrile–0.1 % formic acid and the solvent extract is directly injected into an Acquity BEH Amide column (2.1 × 100 mm, 1.7 μm) operating in HILIC mode at 0.2 mL/min with 80:20 acetonitrile–0.1 % formic acid in water. The analyte is separated by an organic solvent gradient and quantified by an Agilent Ultivo triple quadrupole mass spectrometer operating in multiple reaction monitoring (MRM) mode. The quantitative MRM transitions were m/z 762→234 and m/z 765→234 for trabectedin and its d3-labeled derivative, respectively. The lower limit of quantification (LLOQ) was 0.01 ng/mL and the assay was linear up to 2.5 ng/mL. The intra- and inter-day relative error ranged from 1.19 % to 8.52 %, while the relative standard deviation was less than 12.35 %. The method was used to determine the pharmacokinetic profiles of trabectedin in 26 patients with soft tissue sarcoma, showing that this new HILIC-MS/MS method is suitable for use in clinical research.
AB - Few time-consuming bioanalytical methods are currently available for trabectedin quantification in clinical investigations. Here we present a novel, fast and sensitive method for trabectedin determination in human plasma based on hydrophilic interaction liquid chromatography and tandem mass spectrometry (HILIC-MS/MS). Plasma samples are treated with acetonitrile–0.1 % formic acid and the solvent extract is directly injected into an Acquity BEH Amide column (2.1 × 100 mm, 1.7 μm) operating in HILIC mode at 0.2 mL/min with 80:20 acetonitrile–0.1 % formic acid in water. The analyte is separated by an organic solvent gradient and quantified by an Agilent Ultivo triple quadrupole mass spectrometer operating in multiple reaction monitoring (MRM) mode. The quantitative MRM transitions were m/z 762→234 and m/z 765→234 for trabectedin and its d3-labeled derivative, respectively. The lower limit of quantification (LLOQ) was 0.01 ng/mL and the assay was linear up to 2.5 ng/mL. The intra- and inter-day relative error ranged from 1.19 % to 8.52 %, while the relative standard deviation was less than 12.35 %. The method was used to determine the pharmacokinetic profiles of trabectedin in 26 patients with soft tissue sarcoma, showing that this new HILIC-MS/MS method is suitable for use in clinical research.
KW - Cancer
KW - HILIC
KW - LC-MS/MS
KW - Pharmacokinetics
KW - Trabectedin
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UR - http://www.scopus.com/inward/citedby.url?scp=85082480467&partnerID=8YFLogxK
U2 - 10.1016/j.jpba.2020.113261
DO - 10.1016/j.jpba.2020.113261
M3 - Article
C2 - 32229403
AN - SCOPUS:85082480467
VL - 185
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
SN - 0731-7085
M1 - 113261
ER -