Journal
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Volume 1163, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jchromb.2020.122498
Keywords
UPLC-MS; Quantification; D-pinitol; Pharmacokinetic; Bioavailability
Funding
- National Natural Science Foundation of China [81773691, 81703815]
- Wenzhou Science and Technology Major Project, China [ZS2017018]
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This study developed a sensitive and rapid method for determining and studying the pharmacokinetics of D-pinitol in rat plasma, showing that D-pinitol has a slow elimination phase and a potential high affinity binding to blood protein in vivo.
D-pinitol could be a potential therapeutic agent for the treatment of diabetes mellitus (DM) type II. In this work, a sensitive and rapid ultra performance liquid chromatography coupled with tandem mass spectrometry method was firstly developed and validated for the determination and pharmacokinetic study of D-pinitol in rat plasma. D-pinitol and 5,7-dihydroxychromone (Internal Standard, IS) were completely separated on a BEH C18 column. The plasma samples were deproteinated with acetonitrile: ethanol (1:1). The MRM transitions for D-pinitol was m/z 179.125 -> 105.049, and for IS was m/z 195.085 -> 109.031. The method linearity ranges was 5-200 ng/mL. The precision, accuracy, recovery, matrix effect, stability under different conditions, were all within the required criteria. After intragastric (50 mg/kg) administration of D-pinitol to the rats, the maximum plasma concentration (C-max) was 77.8 +/- 19.5 ng/mL. The time to reach the maximum plasma concentration (T-max) was 2.2 +/- 0.98 h. Apparent distribution volume (V-z) was 1557.5 +/- 1329.1 L/kg and the plasma centration time curve (AUC(0-t)) was 1265.5 +/- 479.3 mu g/L*h. After intravenous (5.0 mg/kg) administration, V-z was 325.2 +/- 107.8 L/kg and AUC((0-t)) was 693.0 +/- 89.9 mu g/L*h. Our study indicated D-pinitol had a slow elimination phase and might be the high affinity binding to blood protein in vivo, which are helpful for its further drug development and clinical application.
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