The rapid and sensitive method for quantifying mebeverine metabolites in human plasma was developed using HPLC-MS/
MS. Mebeverine acid-D5 and desmethyl mebeverine acid-D5 were used as internal standards. Sample preparation was
performed by protein precipitation. The chromatographic separation was achieved on Phenomenex Luna C8 Mercury (20 x
4.0 mm, 5 μm) and Phenomenex Luna 5u C8 (150 x 4.6 mm, 5 μm) under gradient conditions of mobile phase. The calibration
range of mebeverine acid and desmethyl mebeverine acid was 10 – 2000 ng/ml. The method was applied to conduct a
pharmacokinetic study of 200 mg prolonged-release capsules Duspatalin on 24 healthy participants.
Mebeverine is myotropic antispasmodic agent which effect is
based on blockade of fast sodium channels and slow calcium
channels on membrane of myocytes. It slows down depolarization
of the membrane and prevents contraction of muscle
fibers. The drug has high selectivity to smooth muscles of the
gastrointestinal tract. Therefore it is primarily used to relieve
spasms of organs of the digestive system.
Mebeverine being an ester is rapidly hydrolyzed in step of
first-pass elimination by esterases to 3.4-dimethoxybenzoic
(veratric) acid and mebeverine alcohol. The main metabolites
of the drug are mebeverine acid (MA) and desmethyl mebeverine
acid.
The half-life of DMA after administration of prolonged-release
capsules of mebeverine is 5-6 h, maximum concentration in
blood (Cmax) after a single dose is 679 ng/ml, after repeated
doses 804 ng/ml, time-to-peak concentration (Tmax) is about
2.92 hours. The area under the curve “concentrationtime”
from last blood sampling procedure (AUC0-t) for DMA is
4552 ng∙h/mL, the elimination constant is 0.147. The values
of pharmacokinetic parameters for MA were not published.
Therefore, obtaining new data about pharmacokinetic of mebevere in the form of prolonged-release capsule is actual.
Several analytical methods of quantitative determination of
mebeverine metabolites in plasma using HPLC and HPLC-MS/
MS were reported. However, these methods have some
disadvantages, such as necessity of complex sample preparation,
using solid-phase and liquid-liquid extraction, and lack of
sensitivity (high LLOQ).
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