An Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC–MS/MS) Method for Qualifying DAPB in Rat Plasma and Application to Pharmacokinetic Studies
Bei Qin,
Yunmei Chen,
Kuan Yang,
Rong Wang,
Lili Yu,
Nana Wang,
Shaojing Liu
Affiliations
Bei Qin
Xi’an Key Laboratory for Research and Development of Innovative Multi-Target Antihypertensive Drugs, Xi’an Innovative Antihypertensive Drugs International Science and Technology Cooperation Base, Xi’an Medical University, Xi’an 710021, China
Yunmei Chen
Xi’an Key Laboratory for Research and Development of Innovative Multi-Target Antihypertensive Drugs, Xi’an Innovative Antihypertensive Drugs International Science and Technology Cooperation Base, Xi’an Medical University, Xi’an 710021, China
Kuan Yang
Xi’an Key Laboratory for Research and Development of Innovative Multi-Target Antihypertensive Drugs, Xi’an Innovative Antihypertensive Drugs International Science and Technology Cooperation Base, Xi’an Medical University, Xi’an 710021, China
Rong Wang
Xi’an Key Laboratory for Research and Development of Innovative Multi-Target Antihypertensive Drugs, Xi’an Innovative Antihypertensive Drugs International Science and Technology Cooperation Base, Xi’an Medical University, Xi’an 710021, China
Lili Yu
Xi’an Key Laboratory for Research and Development of Innovative Multi-Target Antihypertensive Drugs, Xi’an Innovative Antihypertensive Drugs International Science and Technology Cooperation Base, Xi’an Medical University, Xi’an 710021, China
Nana Wang
Xi’an Key Laboratory for Research and Development of Innovative Multi-Target Antihypertensive Drugs, Xi’an Innovative Antihypertensive Drugs International Science and Technology Cooperation Base, Xi’an Medical University, Xi’an 710021, China
Shaojing Liu
Xi’an Key Laboratory for Research and Development of Innovative Multi-Target Antihypertensive Drugs, Xi’an Innovative Antihypertensive Drugs International Science and Technology Cooperation Base, Xi’an Medical University, Xi’an 710021, China
DAPB, a new molecule including danshensu, borneol, and a mother nucleus of ACEI (Angiotensin-converting enzyme inhibitors), is being developed as an antihypertensive candidate compound. A rapid, accurate, and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was established and validated for the determination of DAPB in rat plasma. Chromatographic separation was performed on an Agilent SB-C18 column after protein precipitation by acetonitrile with a mobile phase consisting of acetonitrile and deionized water with 0.02% formic acid and 5 mM NH4F (v/v) at a flow rate of 0.2 mL/min. Quantification was performed using electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The method was linear over the range of 2–1000 ng/mL. The intra- and inter-day precision was within 12%, with accuracies less than 7%. Stability was within the acceptable limits under various storage and processing conditions. No apparent matrix effect was detected. The validated method was applied to the pre-clinical pharmacokinetic study of DAPB after oral administration of 30 mg/kg and intravenous administration of 6 mg/kg in rats.
