Development and Application of an LC-MS/MS Method for the Detection of Alectinib and its Impurity 5-Trifluoroacetate in Bulk and Formulation Analyses: Evaluation of the Greenness, Whiteness, and Blueness of the Method

LEVENT S., AVCI H., Elris A., ÖZCAN S., CAN N. Ö.

CURRENT ANALYTICAL CHEMISTRY, 2026 (SCI-Expanded, Scopus)

Özet

Introduction Alectinib is approved for the treatment of patients with unresectable, advanced, or recurrent non-small cell lung cancer that is positive for the ALK fusion gene. Alectinib impurity-5, also known as alectinib impurity 5-trifluoroacetate, is one of alectinib's impurities that is commercially available. In this work, a sensitive and simple LC-MS/MS method for the simultaneous analysis of alectinib and alectinib impurity-5 was developed and validated. Methods Chromatographic analyses were performed in isocratic mode, a SunShell (R) C18 (90 & Aring;, 2.6 & micro;m, 4,6 & times;150 mm) column was used as the stationary phase, and the mobile phase used was 5 mM ammonium acetate buffer at pH 5.5 (A) and acetonitrile (B) in the ratio of 30:70 (v/v) with the flow rate of 0.55 mL/min. A triple quadrupole LC-MS/MS equipment was used for the detection; the mass transition ion pair was determined to be m/z 483.35 -> 396.30 for alectinib and m/z 501.40 -> 414.15 for impurity-5.Results The calibration curve was within the ranges of 2.5-100 ng/mL for alectinib and 5.0-200.0 ng/mL for impurity-5. LOD and LOQ levels were calculated for alectinib and impurity-5 as 0.83 and 2.50 ng/mL, and 1.66 and 5.00 ng/mL, respectively. Alectinib recovery values ranged from 98.5% to 101.0%, whereas impurity-5 recovery values ranged from 95.56% to 95.8%.Discussion During the optimization process, various column types, mobile phase compositions and ratios, flow rates, and injection volumes were examined in detail to establish optimum conditions. The method was fully validated, and the required parameter limits were successfully met. In addition, the developed method was evaluated using various metrics to ensure it is green, sustainable, and practical within methodological limits. Conclusion Laboratories equipped with LC-MS/MS systems can easily apply this method for quality control analyses. Moreover, the method is fast, reliable, and environmentally friendly, providing all the qualities and features recommended by the ICH guide.