Fast Analysis of Terbutaline in Pharmaceuticals by CE-MS/MS

Significance of the Topic

Terbutaline is a β2-adrenergic agonist used in asthma relief and to delay preterm labor. Reliable quantification of terbutaline in diverse pharmaceutical forms such as syrups, inhalants, and injectables is critical for quality control, patient safety, and regulatory compliance.

Objectives and Study Overview

This work aimed to develop and validate a rapid capillary electrophoresis–tandem mass spectrometry (CE-MS/MS) method for determining terbutaline in pharmaceutical syrups. The method was benchmarked against the British Pharmacopoeia’s HPLC protocol to assess accuracy, sensitivity, and speed.

Methodology and Instrumentation

Sample Preparation:

• Syrup samples homogenized and diluted 1:100 in background electrolyte (BGE).
• Filtration through 0.2-µm PVDF/PP cartridges.

CE-MS/MS Conditions:

• Background electrolyte: 25 mM propionic acid + 25 mM ammonium hydroxide (pH 7.0).
• Capillary: fused silica, 50 µm i.d., 60 cm length, 25 kV, 25 °C.
• Injection: hydrodynamic, 50 mbar for 10 s.
• Sheath liquid: BGE diluted 1:4 in H2O/methanol (1:1), 5 µL/min.
• MS in positive ESI MRM mode, two transitions (m/z 226→152 for quantification, 226→107 for confirmation).

Used Instrumentation:

• Agilent 7100 CE system
• Agilent 6430 triple quadrupole mass spectrometer

Main Results and Discussion

• Migration time for terbutaline: ~3.4 min, total run under 5 min.
• Linearity over 0.05–50 µg/mL, correlation coefficient R² > 0.999.
• Limit of detection: 0.01 µg/mL; limit of quantification: 0.03 µg/mL.
• Analysis of two commercial syrup samples yielded 299.0–300.2 µg/mL by CE-MS/MS vs. 300.0–301.0 µg/mL by HPLC, confirming accuracy and precision.

Advantages and Practical Applications

The CE-MS/MS protocol offers rapid analysis, high sensitivity, minimal sample and reagent consumption, and simplified sample preparation without extensive cleanup. Its specificity and quantitative performance make it suitable for routine QC in pharmaceutical development and manufacturing laboratories.

Future Trends and Potential Applications

• Extension to other β-adrenergic drugs and combination formulations.
• Miniaturization and green CE approaches to further reduce solvent use.
• Integration with high-throughput workflows and automated sample handling.
• Application in bioanalytical and clinical pharmacokinetic studies.

Conclusion

The developed CE-MS/MS method provides a fast, sensitive, and accurate alternative to conventional HPLC for terbutaline quantification in pharmaceutical syrups. Its robustness and low resource consumption support broader adoption in quality control and research settings.

References

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