Abstract |
A liquid chromatographic/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 approximately 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 degrees 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 degrees C. Additional variations in plasma concentration of the analyte due to the use of different sources of plasma were also evaluated.
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Authors | J J Zhao, I Xie, J D Rogers |
Journal | Journal of mass spectrometry : JMS
(J Mass Spectrom)
Vol. 34
Issue 10
Pg. 1018-27
(Oct 1999)
ISSN: 1076-5174 [Print] England |
PMID | 10510424
(Publication Type: Journal Article)
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Copyright | Copyright 1999 John Wiley & Sons, Ltd. |
Chemical References |
- Endothelin Receptor Antagonists
- Indicators and Reagents
- Pyridines
- J 104132
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Topics |
- Calibration
- Chromatography, Liquid
- Endothelin Receptor Antagonists
- Humans
- Indicators and Reagents
- Mass Spectrometry
- Pyridines
(blood)
- Reproducibility of Results
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