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Validation and application of a simple reverse phase HPLC method for in vitro dissolution studies of memantine hydrochloride tablet

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Abstract

A simple, accurate and cost-effective ultraviolet-high performance liquid chromatography (UV-HPLC) assay method was developed and validated for the determination of derivatized memantine, a representative oral noncompetitive N-methyl-d-aspartate receptor antagonist to treat Alzheimer’s disease, in dissolution medium. Optimized derivatization process of memantine was performed with 9-fluorenylmethyl-chloroformate (FMOC), and injected with the UV-HPLC system for quantitation. Derivatized memantine were separated on a reverse phase C18 column (Shiseido, 250 × 4.6 mm, 5 μm) with a mixture of 50 mM phosphate buffer (pH 4, adjusted with orthophosphoric acid) and Acetonitrile (20:80, v/v), at a flow rate of 2.0 mL/min. UV detection was monitored at 265 nm. The detector response was specific and linear over the concentration range of 1.0–20.0 μg/mL. Validation parameters of derivatized memantine with the sensitivity, selectivity, linearity, accuracy, precision and stability in dissolution medium (pH 1.2) were acceptable based on International Conference on Harmonization Q2 (R1). The assay method validated in this work was successfully applied for a dissolution study of a commercial tablet containing memantine hydrochloride (i.e., Ebixa®, 10 mg). Thus, the developed method would be appropriate for routine in vitro dissolution studies of memantine hydrochloride tablet.

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Abbreviations

ACN:

Acetonitrile

AD:

Alzheimer’s disease

FMOC:

9-Fluorenylmethyl-chloroformate

FDNB:

1-Fluoro-2,4-dinitrobenzene

HPLC:

High-performance liquid chromatography

LOQ:

Limit of quantification

NMDA:

N-methyl-d-aspartate

QC:

Quality control

RSD:

Relative standard deviation

SPE:

Solid-phase extraction

UV:

Ultraviolet

References

  • Farlow MR (2004) NMDA receptor antagonists. A new therapeutic approach for Alzheimer’s disease. Geriatrics 59:22–27

    PubMed  Google Scholar 

  • Haen E, Koeber R, Klünemann HH, Waimer R, Köstlbacher A, Wittmann M, Brandl R, Dörfelt A, Jahner T, Melchner D (2012) Implementation of a cost-effective HPLC/UV approach for routine medical quantification of memantine in human serum. Ther Drug Monit 34:702–712

    Article  CAS  PubMed  Google Scholar 

  • Hassan MG, Emara KM, Mohamed HA, Abdel-Wadood HM, Ikeda R, Wada M, Kuroda N, Nakashima K (2012) Determination of memantine in rat plasma by HPLC-fluorescence method and its application to study of the pharmacokinetic interaction between memantine and methazolamide. Biomed Chromatogr 26:214–219

    Article  CAS  PubMed  Google Scholar 

  • Higashi Y, Nakamura S, Matsumura H, Fujii Y (2006) Simultaneous liquid chromatographic assay of amantadine and its four related compounds in phosphate-buffered saline using 4-fluoro-7-nitro-2,1,3-benzoxadiazole as a fluorescent derivatization reagent. Biomed Chromatogr 20:423–428

    Article  CAS  PubMed  Google Scholar 

  • Jalalizadeh H, Raei M, Tafti RF, Farsam H, Kebriaeezaheh A, Souri E (2013) A Stability-indicating HPLC method for the determination of memantine Hydrochloride in dosage forms through derivatization with 1-fluoro-2,4-dinitrobenzene. Sci Pharm 82:265–279

    Article  PubMed Central  PubMed  Google Scholar 

  • Michail K, Daabees H, Beltagy Y, Elkhalek MA, Kharmis M (2013) High-performance liquid chromatographic determination of memantine in human urine following solid-phase extraction and precolumn derivatization. J AOAC Int 96:1302–1307

    Article  CAS  PubMed  Google Scholar 

  • Narola B, Singh AS, Santhakumar PR, Chandrashekhar TG (2010) A validated stability-indicating Reverse Phase HPLC Assay method for the determination of memantine hydrochloride drug substance with UV-detection using precolumn derivatization technique. Anal Chem Insights 5:37–45

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Parsons CG, Danysz W, Quack G (1999) Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist–a review of preclinical data. Neuropharmacology 38:735–767

    Article  CAS  PubMed  Google Scholar 

  • Ponnayyan Sulochana S, Sharma K, Mullangi R, Sukumaran SK (2014) Review of the validated HPLC and LC-MS/MS methods for determination of drugs used in clinical practice for Alzheimer’s disease. Biomed Chromatogr 28:1431–1490

    Article  CAS  PubMed  Google Scholar 

  • Puente B, Hemandez E, Perez S, Pablo L, Prieto E, Garcia MA, Bregante MA (2011) Determination of memantine in plasma and vitreous humour by HPLC with precolumn derivatization and fluorescence detection. J Chromatogr Sci 49:745–752

    Article  CAS  PubMed  Google Scholar 

  • Santa T (2014) Recent advances in development and application of derivatization reagents having a benzofurazan structure: a brief overview. Biomed Chromatogr 28:760–766

    Article  CAS  PubMed  Google Scholar 

  • Tekkeli SE, Toker SE (2013) A new HPLC method with fluorescence detection for the determination of memantine in human plasma. J AOAC Int 96:52–55

    Article  CAS  PubMed  Google Scholar 

  • Toker SE, Sagirli O, Cetin SM, Önal A (2011) A new HPLC method with fluorescence detection for the determination of memantine in human plasma. J Sep Sci 34:2645–2649

    Article  CAS  PubMed  Google Scholar 

  • Xie MF, Zhou W, Tong XY, Chen YL, Cai Y, Li Y, Duan GL (2011) High-performance liquid chromatographic determination of memantine hydrochloride in rat plasma using sensitive fluorometric derivatization. J Sep Sci 34:241–246

    Article  CAS  PubMed  Google Scholar 

  • Zarghi A, Shafaati A, Foroutan SM, Khoddam A, Madadian B (2010) Sensitive and rapid HPLC method for determination of memantine in human plasma using OPA derivatization and fluorescence detection: application to pharmacokinetic studies. Sci Pharm 78:847–856

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This article does not contain any studies with human and animal subjects performed by any of the authors. And all authors (H.-J. Maeng, S.-U. Choi, J.-Y. Yoon, D.-J. Jang, D. W. Lee, B.-N. Ahn, M.-K. Choi, I.-S. Song, K. H. Cho) declare that they have no conflict of interest. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2014R1A1A1002828).

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    Authors and Affiliations

    1. College of Pharmacy, Gachon University, 191, Hambakmoeiro, Yeonsu-gu, Incheon, 406-799, South Korea

      Han-Joo Maeng

    2. Department of Food Science & Biotechnology, Dongnam Health University, 50, Cheoncheonro, Suwon, 440-714, South Korea

      Sung-Up Choi

    3. Department of Pharmaceutical Engineering, Inje University, 197, Injero, Gimhae, 621-749, South Korea

      Dong-Jin Jang

    4. Central Research Institute, Whan In Pharmaceutical Co. Ltd., Suwon, 443-766, South Korea

      Dong Won Lee & Byung-Nak Ahn

    5. College of Pharmacy, Dankook University, 119, Dandaero, Cheonan, 330-714, Chungnam, South Korea

      Min-Koo Choi

    6. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80, Daehakro, Daegu, 702-701, South Korea

      Im-Sook Song

    7. College of Pharmacy, Inje University, 197, Injero, Gimhae, Gyeongnam, 621-749, Republic of Korea

      Kwan Hyung Cho

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    Correspondence to Kwan Hyung Cho.

    Additional information

    Han-Joo Maeng and Sung-Up Choi have contributed equally to this work.

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    Maeng, HJ., Choi, SU., Jang, DJ. et al. Validation and application of a simple reverse phase HPLC method for in vitro dissolution studies of memantine hydrochloride tablet. Journal of Pharmaceutical Investigation 45, 415–421 (2015). https://doi.org/10.1007/s40005-015-0184-1

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    • DOI: https://doi.org/10.1007/s40005-015-0184-1

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