Moustapha E Moustapha1,2,
Sherif A Abdel-Gawad3,4 
For correspondence:- Sherif Abdel-Gawad Email: sagawad@yahoo.com
Accepted: 24 May 2020 Published: 30 June 2020
Citation: Moustapha ME, Abdel-Gawad SA. Solid phase extraction and LC-MS/MS quantification of ibandronate in human plasma. Trop J Pharm Res 2020; 19(6):1295-1302 doi: 10.4314/tjpr.v19i6.26
© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
Purpose: To develop and validate a simple, highly sensitive and accurate method for the quantification of ibandronate (IBN) in human plasma.
Methods: Electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS) in positive ion mode was applied to obtain optimum signals. The parent ion was acquired under collision-activated dissociation conditions, and the abundant fragments used to design multiple reaction monitoring experiments for monitoring two ibandronate transitions (m/z 376 to m/z 114, and m/z 376 to m/z 250). The IBN was isolated from plasma with weak anion exchange solid phase extraction columns with ‘on-cartridge’ derivatization using tri-methylsilyl-diazomethane (TMSDZ) reagent to convert IBN to tetra-methyl derivative.
Results: The studied drug was successfully extracted from plasma samples without any interference at a retention time of 3.2 min. The matrix effect averaged 110 %, indicating that endogenous materials had little effect on ionization. The relationship between plasma analyte concentration and IBN signal area was satisfactorily linear, with correlation coefficient (r2) ranging from 0.9817 to 0.9942 in the concentration range of 0.5 – 200 ng/ml. The lower and upper limits of quantification (LLOQ and ULOQ) for IBN were 0.5 and 200 ng/ml, respectively. Relative recovery of IBN from plasma after extraction and derivatization at 3 distinct concentrations was 83.93 to 85.06 %, relative to standard solutions. The ranges of intra- and inter-day accuracies of quantification of quality controls were 89.39 - 106.40 %, and 90.50 - 107.96 %, respectively. Processed plasma IBN extracts were stable in autosampler at 4 0C (91.12 to 103.49%). Long-term stability in plasma after 30 days at -24 0C ranged from 89.52 to 113.18 %.
Conclusion: This validated LC-MS/MS method can be successfully applied for determination of IBN in pharmacokinetic studies. It is a sensitive and specific assay for plasma IBN in bioequivalence studies.
Archives
News Updates
Fulltext in PDF