Abstract
Y-99, a promising first-in-class diuretic, is a novel urea transporter inhibitor with oral diuretic activity. However, little is known about the pharmacokinetic profiles of Y-99 in experimental animals. In this study, a method of quantitative determination of Y-99 in rat plasma based on high-performance liquid chromatography-tandem mass spectrometry was developed and validated in selectivity, linearity, recovery and matrix effect, accuracy and precision, stability, carry-over and dilution integrity. Chromatographic separation was conducted on an ACQUITY BEH C18 column (2.1mm × 50mm, 1.7μm) with gradient elution at a 0.3mL/min flow rate after protein precipitation. Mass spectrometry was performed by a positive electrospray ionization mass spectrometer in multiple reaction monitoring mode. The method showed standard-compliant linearity (1-1,000ng/mL, r = 0.9991). The intra-day and inter-day accuracy (relative error < 11.2%) and precision (coefficient of variation <8.4%) were within acceptable criteria. The recovery and matrix effects were 97.3-110.7% and 103.7-107.5%, respectively. The stability, dilution integrity and carry-over of the method were also within the acceptable criteria. Pharmacokinetic profiles of Y-99 in rats were first investigated using this method, which was vital for developing novel diuretics without electrolyte imbalance targeting urea transporters.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.