TITLE:
Determination of Rizatriptan in Human Plasma by LC-MS/MS
AUTHORS:
Nihal Saraner, Barış Şenceol, Ayşen Bakıcı, Berrak Güney, Onursal Sağlam
KEYWORDS:
Rizatriptan, Rizatriptan-D6, Human Plasma, LC-MS/MS
JOURNAL NAME:
Open Journal of Applied Sciences,
Vol.16 No.9,
September
10,
2026
ABSTRACT: A selective LC-MS/MS method was developed and comprehensively validated for the quantification of rizatriptan in human plasma, employing protein precipitation as the sample preparation technique. Chromatographic separation was achieved on a GL Sciences InertSustain AQ C18 column (3 μm, 4.6 × 75 mm) under isocratic conditions and detection was performed by multiple reaction monitoring (MRM) in positive electrospray ionization mode. Rizatriptan-D6 was employed as the internal standard. No significant endogenous interference was observed at the retention times corresponding to rizatriptan or the internal standard, confirming the selectivity of the analytical method. The calibration model demonstrated linearity over the concentration range of 0.25 - 60 ng/mL using weighted (1/C2) linear regression. Accuracy and precision results complied with the predefined acceptance criteria across all evaluated concentration levels and validation batches. The protein precipitation procedure provided consistent extraction performance and recovery of rizatriptan and the internal standard. No significant matrix-related effects or carry-over were observed indicating that neither factor adversely affected the quantitative determination of rizatriptan. Rizatriptan also demonstrated satisfactory stability under all investigated conditions, including bench-top, freeze-thaw, autosampler, whole-blood, stock solution, working solution and long-term storage conditions. The method involved a simple sample preparation procedure and a short chromatographic run time of 2.5 min, allowing plasma samples to be analyzed rapidly. The validated method provides a reproducible approach for the quantification of rizatriptan in human plasma and is suitable for pharmacokinetic, bioequivalence and other quantitative bioanalytical applications.