Overcoming the Charged Ion Competition in Triple Quad Chemical Ionization Ion Source for Estimation of Celecoxib in Biological Matrix and its Application to Bioequivalence Study

Abstract

The purpose of the study was to develop and validate a sensitive, selective and reproducible method for the estimation of Celecoxib in human plasma. During the development, ion competition phenomenon observed in electrospray ionization ion source of liquid chromatography mass spectrometer system and in order to overcome it, different approaches applied. The Celecoxib and Celecoxib D7 in plasma were extracted by liquid-liquid extraction and separated in less than 4.0 min on a reverse phase C₁₈ column, using isocratic elution with a binary mobile phase in the ratio of 70:30 v/v (Acetonitrile: 0.1% Ammonia Solution). Mass spectrometer was used as detector to quantitate the analytes in positive ion mode, using Atmospheric Pressure Chemical Ionization mode. Since the method was developed to perform the pharmacokinetic end point study for United States and Europe market, the method was fully validated, complying Food and Drug Administration, European Medicines Agency guideline and recommendations of American Association of Pharmaceutical Scientists white papers.

Key words

charge competition - celecoxib - human plasma - bioequivalence - pharmacokinetic study

• References

• 1 EMEA scientific discussion for the approval of Onsenal. 2005; https://www.ema.europa.eu/en/documents/scientific-discussion/onsenal-epar-scientific-discussion_en.pdf
• 2 Celebrex Labelling FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020998s017lbl.pdf
• 3 CELEBREX celecoxib capsules Cardiovascular Risk- FDA https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020998s026lbl.pdf
• 4 US. Department of Health and Human Services, Application number NDA 20-998. Pharmacology review(s). https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20998AP_phrmr_P1.pdf
• 5 CELEBREX™ (celecoxib capsules) drug bank https://www.drugbank.ca/drugs/DB00482
• 6 USFDA Draft Guidance on Celecoxib, Recommended Oct 2006; Revised Nov. 2013; https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm083300.pdf
• 7 Emami J, Fallah R, Ajami A. A rapid and sensitive HPLC method for the analysis of celecoxib in human plasma: Application to pharmacokinetic studies. Daru-Journal of Faculty of Pharmacy 2008; 16: 211-217
• 8 Akhtar M, Ahmad M, Ahmad I. et al. Bioequivalence assessment of two formulations of celecoxib: Open label, single dose and two-way cross over study in healthy human male volunteers. African Journal of Pharmacy and Pharmacology 2011; 5: 1773-1777
• 9 Prakasarao Kovvasu Surya, Adireddy Vinayender, Chakravarthy Janjanam Kalyan. A Novel LC-MS/MS method for the determination of celecoxib in human plasma. International Journal of ChemTech Research 2018; 11: 303-311
• 10 Sy-Yeuan Ju, Chen Yun-Chun, Tzeng Hsuan-Kai. et al. Bioequivalence evaluation of two formulations of Celecoxib 200 mg capsules in healthy volunteers by using a validated LC/MS/MS method. Int J Bioanal Methods Bioequival Stud 2015; 2: 34-40
• 11 Park MS, Shim WS, Yim SV. et al. Development of simple and rapid LC-MS/MS method for determination of celecoxib in human plasma and its application to bioequivalence study. J Chromatogr B Analyt Technol Biomed Life Sci 2012; 902: 137-141
• 12 P. Patel Nirav, Sanyal Mallika, S. Shrivastav Pranav. et al. Estimation of celecoxib in human plasma by rapid and selective Lc-Ms/Ms Method for a bioequivalence study. Int J Pharm Pharm Sci 2018; 10: 16-22
• 13 Kushnir M, Rockwood AL, Nelson GL. et al. Assessing analytical specificity in quantitative analysis using tandem mass spectrometry. Clin Biochem. 2005; 38: 319-327
• 14 Bioanalytical Method Validation Guidance for Industry. 2018; https://www.fda.gov/downloads/drugs/guidances/ucm070107.pdf
• 15 Tang K, Jason SP, Richard SD. Charge competition and the linear dynamic range of detection in electrospray ionization mass spectrometry. J Am Soc Mass Spectrom 2004; 15: 1416-1423
• 16 Chambers E, Diehl MDW, Ziling L. et al. Charge systematic and comprehensive strategy for reducing matrix effects in LC/MS/MS analyses. Journal of Chromatography B 2007; 852: 22-34
• 17 Dubey NK, Fozdar BI. Interconversion from N-Desmethyl Clomipramine to Clomipramine and its impact on a bioequivalence study. Sep Sci plus 2018; 1: 714-725
• 18 Jemal M, Ouyang Z, Chen BC. et al. Quantitation of the acid and lactone forms of atorvastatin and its biotransformation products in human serum by high-performance liquid chromatography with electrospray tandem mass spectrometry. Rapid commun. Mass Spectrom 1999; 13: 1003-1015