TY - JOUR

T1 - Comparison of external calibration and isotope dilution LC-ICP-MS/MS for quantitation of oxytocin and its selenium analogue in human plasma

AU - Grønbæk-Thorsen, Freja

AU - Jensen, Camilla

AU - Østergaard, Jesper

AU - Møller, Laura Hyrup

AU - Gammelgaard, Bente

N1 - Publisher Copyright: © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2021

Y1 - 2021

N2 - In the present study, a method for quantitation of the pharmaceutical peptide oxytocin (OT) and its diselenide-containing analogue (SeOT) in human plasma was developed using gradient elution LC-ICP-MS/MS. Plasma samples were precipitated with acetonitrile containing 1.0% TFA in a volume ratio of 1+3 (sample+precipitation agent) before analysis. Post-column isotope dilution analysis (IDA) was applied for quantitation and was compared with external calibration. Both calibration methods appeared to be fit for purpose regarding figures of merit including linearity, precision, LOD, LOQ and recovery. Analysis of OT and SeOT showed that selenium-based analysis is considerably more sensitive and selective compared to the sulfur-based analysis. Despite the relatively simpler setup of external calibration, IDA can be advantageous because it compensates for instrument drift and changes in organic solvent concentration. The method was applied for a stability study showing the degradation of OT and SeOT in plasma. The degradation of SeOT was faster than the degradation of OT in plasma. Thus, possible stability effects should be considered before replacing a disulfide bridge with a diselenide bridge or introducing a diselenide label in a potential drug. Graphical abstract: [Figure not available: see fulltext.]

AB - In the present study, a method for quantitation of the pharmaceutical peptide oxytocin (OT) and its diselenide-containing analogue (SeOT) in human plasma was developed using gradient elution LC-ICP-MS/MS. Plasma samples were precipitated with acetonitrile containing 1.0% TFA in a volume ratio of 1+3 (sample+precipitation agent) before analysis. Post-column isotope dilution analysis (IDA) was applied for quantitation and was compared with external calibration. Both calibration methods appeared to be fit for purpose regarding figures of merit including linearity, precision, LOD, LOQ and recovery. Analysis of OT and SeOT showed that selenium-based analysis is considerably more sensitive and selective compared to the sulfur-based analysis. Despite the relatively simpler setup of external calibration, IDA can be advantageous because it compensates for instrument drift and changes in organic solvent concentration. The method was applied for a stability study showing the degradation of OT and SeOT in plasma. The degradation of SeOT was faster than the degradation of OT in plasma. Thus, possible stability effects should be considered before replacing a disulfide bridge with a diselenide bridge or introducing a diselenide label in a potential drug. Graphical abstract: [Figure not available: see fulltext.]

KW - Inductively coupled mass spectrometry

KW - Isotope dilution analysis

KW - Liquid chromatography

KW - Peptide quantitation

KW - Se labelling

U2 - 10.1007/s00216-021-03611-1

DO - 10.1007/s00216-021-03611-1

M3 - Journal article

C2 - 34458946

AN - SCOPUS:85113771266

VL - 413

SP - 6479

EP - 6488

JO - Analytical and Bioanalytical Chemistry

JF - Analytical and Bioanalytical Chemistry

SN - 1618-2642

ER -