AN LC-MS/MS BASED BIOANALYTICAL APPROACH TO RESOLVE PHARMACOKINETIC INVESTIGATION OF ACOTIAMIDE HYDROCHLORIDE AND ITS APPLICATION TO BIOEQUIVALENCE STUDY

  • DHIMAN HALDER Bioequivalence Study Centre, Jadavpur University, Kolkata
  • SOURAV DAS TAAB Biostudy Services, Kolkata, India
  • BALARAM GHOSH Midnapore Medical College, Midnapore
  • EASHA BISWAS Bioequivalence Study Centre, Jadavpur University, Kolkata
  • SUKANTA ROY TAAB Biostudy Services, Kolkata, India
  • ANIRBANDEEP BOSE TAAB Biostudy Services, Kolkata, India
  • NAVJOT SINGH Nri Institute of Pharmacy, Bhopal
  • TAPAN KUMAR PAL Bioequivalence Study Centre, Jadavpur University, Kolkata, TAAB Biostudy Services, Kolkata, India

Abstract

Objective: Acotiamide, a prokinetic drug used to treat Functional Dyspepsia, which acts by modulating gastric motility. However, in this present study, a simple and accurate bioanalytical method was developed for the estimation of Acotiamide in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and validated according to US-FDA guideline.


Methods: The method was developed in blank human blood plasma; propranolol was used as internal standard (IS). Protein Precipitation technique was followed for the extraction of the drug from the plasma sample. In liquid chromatography, the C18 analytical column (50 x 3 mm, particle size-5 μm) was used; as a mobile phase, 0.1% formic acid in Mili Q water, and ACN with methanol (1:1) used, at 0.50 ml/min flow rate. Detection was done by positive electrospray ionization (ESI) with a run time of 7 min in multiple reaction monitoring (MRM) mode. Eight calibration concentrations were taken, ranging from 1.5625-200 ng/ml for Acotiamide. Different stability studies were performed and obtained results found within the acceptable range. Moreover, a comparative pharmacokinetic analysis was done in 24 healthy human volunteers in a single dose, randomized, crossover study.


Results: The precursor to production reaction was; m/z 451.200 → 271.200 for Acotiamide and m/z 260.300 → 116.100 m/z for IS. The obtained calibration curve was linear, with a mean r2value 0.9953. Among the pharmacokinetic parameters, Cmax and Tmax were 25.71±2.31,23.61±2.32 ng/ml; 2.54±0.12, 2.43±0.21 h for reference and test samples, respectively.


Conclusion: No major adverse events were noted in the clinical phase, the developed method was accurate and linear; obtained pharmacokinetic parameters hence represented.

Keywords: Acotiamide, LC-MS/MS, Pharmacokinetics, Bioequivalence, Mass spectrometry, US-FDA guideline

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HALDER, D., S. DAS, B. GHOSH, E. BISWAS, S. ROY, A. BOSE, N. SINGH, and T. K. PAL. “AN LC-MS/MS BASED BIOANALYTICAL APPROACH TO RESOLVE PHARMACOKINETIC INVESTIGATION OF ACOTIAMIDE HYDROCHLORIDE AND ITS APPLICATION TO BIOEQUIVALENCE STUDY”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 12, no. 10, Sept. 2020, pp. 76-84, doi:10.22159/ijpps.2020v12i10.38410.
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