Comparison of three triterpenoids' pharmacokinetic characteristics using UHPLC-MSMS after oral administration of a cucurbitacin tablet and nanosuspension

Abstract

Cucurbitacin, a triterpenoid chemical derived from Pedicellus Melo, is the principal active ingredient of cucurbitacin
tablets (CUT) prescribed for the treatment of primary liver cancer and chronic hepatitis. Oral bioavailability of
pharmacopotent compounds may be enhanced using nanosuspensions. The pharmacokinetics of three cucurbitacin
triterpenoids (CuB, CuD, and CuE) after oral administration of CUT and a new P. Melo nanosuspension (MP-NPs)
in rats have never been studied before.
Methods: The amounts of these cucurbitacin triterpenoids in the plasma were measured using UHPLC-MS/MS,
which stands for ultra-performance liquid chromatography-tandem mass spectrometry. Using the positive ion mode
for multiple reaction monitoring analysis, a sensitive, easy-to-use, and selective UHPLC-MS/MS technique was
created. Waters Acquity HSS T3 (1.8 μm, 2.1 × 100 mm) was the chromatographic column used; the column
temperature was 35 °C, and the flow rate was
0.3 mL/min, 5 μL injection volume, and a gradient elution of water (A) and methanol (B) was used as the mobile
phase. The accuracy varied from -6.41% to -4.01% and the intra- and inter-day precision for all analytes was less
than 13%. The data show that when the two groups of rats were given the same amount of CUT and MP-NPs orally,
CuD and CuE had a longer elimination half-life (T1/2) than CuB, suggesting that CuB was eliminated more slowly.
The triterpenoids in the MP-NPs group exhibited a considerable improvement in both Cmax and area under the
plasma concentration compared to the CUT group, and they were able to attain Cmax in only 2 hours.
Discussion: When compared to traditional CUT, the MP-NPs formulation greatly improved the oral bioavailability
of cucurbitacin triterpenoids. These results highlight the promise of nanosuspension technology for enhancing the
pharmacokinetic profile of treatments based on cucurbitacin. Additional research and therapeutic use of cucurbitacin
nanosuspensions may benefit greatly from the findings of this study.