Selective and sensitive method for estimation of liraglutide in human plasma using LCMS-8060

Significance of Topic

The quantification of peptide therapeutics such as liraglutide in human plasma is essential for pharmacokinetic studies, dose optimization and therapeutic monitoring. High sensitivity and selectivity are critical to accurately measure low plasma concentrations, support drug development and ensure patient safety.

Study Objectives and Overview

This work aimed to establish a robust LC–MS/MS assay for selective and sensitive estimation of liraglutide in human plasma. Calibration standards from 0.50 to 200.00 ng/mL and quality controls at multiple levels were employed. The method was validated for key performance characteristics in accordance with regulatory guidelines.

Methodology and Instrumentation

The assay combined protein precipitation and solid-phase extraction for sample cleanup. Key steps included:

• Protein precipitation with methanol, centrifugation, followed by SPE to remove matrix interferences.
• Chromatographic separation on a biphenyl column (100×2.1 mm, 2.7 μm) using gradient elution of aqueous buffer and acetonitrile at 0.25 mL/min.
• Detection on a Shimadzu LCMS-8060 triple quadrupole with heated ESI probe, enabling ultra-fast polarity switching and high desolvation efficiency.

Results and Discussion

Selectivity was confirmed with no interfering peaks in six different blank plasma lots. The assay exhibited linearity (r2 > 0.98) over the calibration range. The lower limit of quantification (LLOQ) was 0.50 ng/mL with signal-to-noise >10. Matrix effects at low and high QC levels were within 3% variability. Intra- and inter-batch precision and accuracy met acceptance criteria (±15% for QCs; ±20% at LLOQ). Mean recovery across QC levels was ~51% with consistent reproducibility. No carry-over was detected in blank injections following the highest calibrator.

Benefits and Practical Applications

This method offers:

• High throughput analysis with minimal sample preparation.
• Enhanced sensitivity for low-concentration measurements critical in pharmacokinetic profiling.
• Reliable performance for bioequivalence, clinical and preclinical studies.

Future Trends and Potential Applications

Emerging trends include integration of automation for SPE processing and further miniaturization of chromatographic systems to increase throughput. Advanced ionization sources and HRMS platforms may expand multiplexed peptide quantitation. Applications could extend to therapeutic peptide panels and personalized medicine monitoring.

Conclusion

The validated LC–MS/MS assay on the Shimadzu LCMS-8060 delivers a selective, sensitive and reproducible approach for liraglutide quantification in human plasma. Its performance aligns with bioanalytical standards and supports pharmacokinetic and therapeutic research.

References

• Liraglutide monograph for professionals. Drugs.com. American Society of Health-System Pharmacists. Retrieved 17 October 2021.
• Structure of liraglutide. Wikipedia. Accessed October 17, 2021.