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Bioanalytical method development, validation and quantification of dorsomorphin in rat plasma by LC-MS/MS
K Karthikeyan1, Mahamad Yunnus A Mahat, S Chandrasekaran
1Bioanalytical-Drug Metabolism and Pharmacokinetics, Drug Discovery Research, R&D Center, Orchid Chemicals and Pharmaceuticals Limited, Sozhanganallur, Chennai, Tamil Nadu, India.
A new liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method accurately measures dorsomorphin in rat plasma. This validated assay enables pharmacokinetic studies of dorsomorphin.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Biotechnology
Background:
- Dorsomorphin is a compound with potential therapeutic applications.
- Accurate quantification of dorsomorphin in biological matrices is crucial for pharmacokinetic studies.
- Existing methods may lack the required sensitivity or specificity for rat plasma analysis.
Purpose of the Study:
- To develop and validate a sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for the quantification of dorsomorphin in rat plasma.
- To establish a reliable analytical tool for pharmacokinetic profiling of dorsomorphin.
Main Methods:
- Development of a sensitive LC-MS/MS method utilizing multiple reaction monitoring (MRM) mode.
- Chromatographic separation on an Agilent XDB C18 column with a mobile phase of acetonitrile and ammonium acetate buffer.
- Zaleplon used as an internal standard for accurate quantification.
- Positive ion mode electrospray ionization (ESI) for detection.
Main Results:
- The developed LC-MS/MS method demonstrated high sensitivity and specificity for dorsomorphin in rat plasma.
- Linearity was established over a concentration range of 0.005 to 10 µg/mL with a correlation coefficient (r²) ≥ 0.99.
- Mean extraction recovery for dorsomorphin and the internal standard exceeded 80%.
- Inter-day and intra-day precision and accuracy were within acceptable limits (85-115% CV).
Conclusions:
- A robust and validated LC-MS/MS method for dorsomorphin estimation in rat plasma has been successfully developed.
- This method is suitable for determining the oral pharmacokinetic profile of dorsomorphin in rats.
- The validated assay provides a valuable tool for preclinical research involving dorsomorphin.
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