Analysis of Underivatized antihistamines

Importance of the topic

The analysis of underivatized antihistamines is critical for pharmaceutical quality control, forensic investigations and clinical studies. These compounds are commonly found in over-the-counter medications and may be subject to abuse or require monitoring in complex biological or environmental samples. Rapid and reliable separation without chemical derivatization streamlines sample preparation and reduces potential artifacts.

Objectives and Study Overview

This application note demonstrates a gas chromatography–flame ionization detection (GC-FID) method for simultaneous determination of eleven underivatized antihistamines and related sympathomimetic agents. The goal is to achieve baseline separation, reproducible retention times and quantitation at 1000 ng/µL level using a single SH-5 Amine capillary column.

Methodology and Instrumentation Used

The method employs a Shimadzu GC system equipped with an FID detector. Key parameters include:

• Column: SH-5 Amine, 30 m × 0.32 mm I.D., 1.00 µm film thickness
• Temperature program: 130 °C initial hold (5 min), ramp at 10 °C/min to 305 °C, final hold 5 min
• Injection: 1 µL split, ratio 1:50, injector temperature 305 °C
• Carrier gas: Hydrogen at 43 cm/s (linear velocity at 130 °C)
• Detector: FID at 305 °C

Main Results and Discussion

The optimized temperature program and amine-selective stationary phase provided clear separation of all target analytes. Eleven compounds—including phenylpropanolamine, ephedrine, pseudoephedrine, pheniramine, diphenhydramine, doxylamine, phenyltoloxamine, methapyrilene, chlorpheniramine, brompheniramine and triprolidine—were resolved with sharp peaks and minimal peak tailing. Retention time reproducibility was within acceptable limits (<1% RSD).

Benefits and Practical Applications

This method offers:

• Elimination of derivatization steps, reducing sample prep time and cost
• High throughput analysis suitable for routine QC and forensic labs
• Robust performance with a wide polarity range of antihistamines

Future Trends and Opportunities

Advancements may include coupling this GC-FID approach with mass spectrometric detection for increased sensitivity and selectivity. Miniaturized columns or fast GC protocols could further shorten analysis time. Integration into automated workflows and development of multiplexed assays for additional drug classes represent promising directions.

Conclusion

The presented GC-FID method on an SH-5 Amine column provides a fast, reliable and derivatization-free assay for underivatized antihistamines. It meets the demands of pharmaceutical QC and forensic applications while offering potential for future enhancements in sensitivity and throughput.