Determination of Midodrine and its Active Metabolite Desglymidodrine by LC-MS/MS and its Application in Human Pharmacokinetic Studies

Author(s): S.T. Narenderan*, S.N. Meyyanathan, B. Babu, Karthik Yamjala, S.J. Ashwini

Journal Name: Current Pharmaceutical Analysis

Volume 15 , Issue 4 , 2019

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Graphical Abstract:


Background: Midodrine (MD) is a prodrug which is converted into Desglymidodrine (DMD) after oral administration.

Objective: The aim of the present study is to develop and validate a precise, accurate liquid chromatography- tandem mass spectroscopy (LC-MS/MS) method for the separation and detection of Midodrine and Desglymidodrine.

Methods: The quantification of prodrug Midodrine (MD) and its active metabolite Desglymidodrine (DMD) in human plasma was performed using simple and economical protein precipitation method. Caffeine was used as an internal standard (IS). LC separation was carried out using Jones C18 column (4.6mm x 150mm, 3µm). Isocratic elution was performed using 10mM ammonium formate (pH 4.0 adjusted with formic acid): methanol 30:70, v/v as a mobile phase, at a constant of flow of 0.5 ml/min.

Results: Mass spectrometric detection was carried out at positive electrospray ionization with proton adducts at m/z 255.0˃237.1, 198.1˃180.2 and 195.0˃138.1 for Midodrine, Desglymidodrine and caffeine (IS) respectively, in MRM mode. The method was validated over a linear concentration range of 0.3-110 ng/ml (r2 =0.996 and r2 =0.9988) for both Midodrine and Desglymidodrine. The recovery of Midodrine and Desglymidodrine were found to be 99 ± 0.12%. The precision (intra-day and inter-day) and accuracy studies fulfilled the acceptance criteria.

Conclusion: The method shows to be stable for the studied stability parameters and was successfully applied for clinical pharmacokinetic studies.

Keywords: Midodrine hydrochloride, desglymidodrine, caffeine, human plasma, pharmacokinetic study, active metabolite.

Gilden, J.L. Midodrine, Adrenergic Agonist and Antagonist. In: Primer on the Autonomic nervous system, 3rd ed; Elsevier, 2012; pp. 621-625.
Midodrine hydrochloride drug details. https://www.drugbank. ca/drugs/DB00211 (Accessed on: November 25, 2016)
Yoshida, H.; Ohno, Y.; Yoshikuni, K.; Todoroki, K.; Nohta, H.; Yamaguchi, M. Determination of midodrine in human plasma by High performance liquid chromatography with fluorescence detection. Anal. Sci., 2003, 19, 317-319.
Barth, T.; Aleu, J. pupo, M.T.; Bonato, P.S.; Collado, I.G. HPLC analysis of midodrine and desglymidodrine in culture medium: Evaluation of static and shaken condition on the biotransformation by fungi. J. Chromatogr. Sci., 2013, 51, 460-467.
Sattar, O.A.; Rezk, M.R.; Badawy, A.M.; Khattab, O.M. Selective determination of midodrine hydrochloride in the presence of its acid degradation product. Anal. Chem., 2013, 12(5), 182-187.
Jain, H.K.; Gujar, K.N.; Randhe, V.A. First order derivative spectrometric method development and validation for Midodrine hydrochloride in bulk and tablets. World J. Pharm. Sci, 2016, 5(7), 1760-1767.
Salunke, S.R.; Damle, M.C. Stability indicating HPTLC for the determination of Midodrine hydrochloride. Eur. J. Pharm. Med. Res., 2016, 3(9), 202-207.
Ali, A.A.; Al-Ghobashy, M.A.; Farid, S.F.; Kassem, M.A. Development and validation of LC-MS/MS method for the determination of the prodrug Midodrine and its active metabolite desglymidodrine in plasma if ascetic patients: Application to individualized therapy and comparative pharmacokinetics. J. Chromtogr. B., 2015, 991, 34-40.
Jia, J.; Gangyi, L.; Li, S.; Wang, Y. Liquid chromatography-tandem mass spectrometry method for the quantification of desglymidodrine in human plasma. J. Pharm. Biomed. Anal., 2006, 40, 715-719.
USFDA -Draft Guidance for industry Bio-analytical method validation. Sep. 2013.. ucm368107.pdf (Accessed on: December 08, 2016)

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Article Details

Year: 2019
Published on: 19 March, 2019
Page: [355 - 362]
Pages: 8
DOI: 10.2174/1573412914666180213125537
Price: $65

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