Alternative analytical methods for ibrutinib quantification in pharmaceutical formulation: A statistical comparison

Abstract

Ibrutinib is a drug used for the treatment of marginal zone lymphoma, mantle cell lymphoma, lymphocytic leukemia, chronic graft, and Waldenstrom macroglobulinemia. A simple, sensitive, and fast liquid chromatographic and spectrophotometric method for the quantification of ibrutinib in pharmaceutical forms and bulk was developed and validated. The chromatographic technique was developed using an ODS 3 C 18 (250 mm × 4.6 mm i.d., 5 µm) column. The mobile phase was a mixture of 0.1% trifluoroacetic acid in water and acetonitrile (50/50, v/v) at a flow rate of 1.0 mL·min−1. Eluent detection was carried out at a wavelength of 260 nm using a ultraviolet detector. The retention time of ibrutinib was found to be 5.27. On the other hand, Ibrutinib was determined using a spectrophotometric technique by measuring the absorbance of the solutions at a wavelength of 260 nm. The developed techniques were validated in accordance with the protocols outlined in International conference on harmonisation of technical requirements for registration of pharmaceuticals for human (ICH) guidelines Q2(R1). Correlation coefficients for both methods were greater than 0.999 in the concentration range of 5–30 mg·mL−1. The relative standard deviation values were low in intraday and interday precision tests. The accuracy of the developed techniques ranged 99.74–100.23% for the chromatographic method and 99.32–100.76% for the spectrophotometric method. The limits of detection and quantitation were 0.90 and 2.80 µg·mL−1 for the chromatographic method and 1.10 and 3.20 µg·mL−1 for the spectrophotometric method. The developed and validated analytical methods can be safely used in quality control tests for the determination of the amount of ibrutinib in pharmaceutical products.

Keywords

• ibrutinib
• method
• development
• validation