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Determination of L‐753,037 in human plasma by liquid chromatography/turbo ionspray tandem mass spectrometry
Author(s) -
Zhao Jamie J.,
Xie Iris,
Rogers J. Douglas
Publication year - 1999
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/(sici)1096-9888(199910)34:10<1018::aid-jms860>3.0.co;2-l
Subject(s) - chemistry , chromatography , calibration curve , analyte , detection limit , extraction (chemistry) , mass spectrometry , tandem mass spectrometry , standard curve , analytical chemistry (journal)
A liquid chromatographyic/turbo ionspray tandem mass spectrometric (LC/MS/MS) method was developed and validated for the determination of L‐753,037, a potent endothelin receptor antagonist currently under development for the treatment of cardiovascular diseases, in human plasma. L‐753,037 is extracted from 0.5 ml of human plasma using liquid–liquid extraction and analyzed by LC/MS/MS with a turbo ionspray interface. Method validation results showed that this method is very sensitive, reliable, selective and reproducible. L‐753,048, an ethoxy analogue of L‐753,037, was used as the internal standard. The method has a lower limit of quantitation (LOQ) of 50 pg ml −1 with a linear calibration range of 0.05–50 ng ml −1 . The intra‐day precision and accuracy ( n = 5) were measured to be below 10% relative standard deviation (RSD) and between 97.4 and 102.8% of the nominal values, respectively, for all calibration standard concentrations within the calibration curve range. The inter‐day precision and accuracy ( n = 3 days, 5 replicates per day) were measured to be below 6.5% RSD and between 99.3 and 102.0% of the nominal values, respectively, for all quality control concentrations. The extraction recovery was determined to be ∼99% on average. The analyte was found to be stable in plasma through three freeze–thaw cycles, for at least 4 h at ambient temperature and for up to 40 days under −20 °C freezer storage conditions. The analyte was also shown to be stable for at least 24 h in the reconstitution solution at room temperature and for up to 3 days as a dried extract at 4 °C. Additional variations in plasma concentration of the analyte due to the use of different sources of plasma were also evaluated. Copyright © 1999 John Wiley & Sons, Ltd.