Analysis of Perindopril Indapamide API

Importance of the Topic

Understanding the composition and purity of perindopril tert‐butylamine combined with indapamide is critical in antihypertensive therapy to ensure efficacy and patient safety. Reliable detection of related impurities at trace levels supports compliance with regulatory standards and quality control in pharmaceutical manufacturing.

Study Objectives and Overview

This application note aims to describe a liquid chromatography method for simultaneous analysis of perindopril tert‐butylamine, indapamide and nine related impurities. The protocol demonstrates a gradient reversed‐phase separation using Shimadzu Shim‐pack Scepter C8 column to achieve baseline resolution and quantification of target compounds at low microgram per milliliter levels.

Methodology and Instrumentation

• Sample preparation
  • Accurately weigh perindopril tert‐butylamine, indapamide and reference impurities I through VI and E
  • Add diluent composed of mobile phase A to B in an 80 to 20 ratio
  • Prepare stock solutions at 1 mg/mL and dilute to 0.03 mg/mL mixed solution for analysis
• Chromatographic system
  • Column Shim‐pack Scepter C8‐120, 5 μm, 250 × 4.6 mm i.d.
  • Mobile phase A: 0.92 g sodium 1‐heptanesulfonate, 1 mL triethylamine and 1.7 g perchloric acid in 1000 mL water adjusted to pH 2.0
  • Mobile phase B: acetonitrile
  • Gradient program: start at 20%B for 5 min, linear to 32%B at 27 min, to 50%B at 45 min, to 80%B at 60–70 min, return to 20%B at 71 min and hold to 80 min
  • Flow rate 1.0 mL/min, column temperature 60 °C, injection volume 20 μL
  • Detection by UV at 210 nm

Main Results and Discussion

The optimized gradient and elevated column temperature provided efficient separation of the API and all impurities. Nine distinct peaks including impurities I through VI and impurity E were resolved with acceptable resolution values. Peak symmetry and retention times were consistent across replicate injections, demonstrating robustness. UV detection at 210 nm enabled sensitive quantification of analytes at low levels.

Benefits and Practical Applications

• Ensures high resolution separation of perindopril, indapamide and related impurities
• Meets stringent regulatory requirements for impurity profiling in pharmaceuticals
• Provides a reliable procedure for routine quality control assays
• Allows trace level detection and quantitation with robust peak performance

Future Trends and Opportunities

Anticipated trends include coupling this method with mass spectrometry for enhanced impurity identification and confirmation. Miniaturization of columns and faster gradients may reduce analysis time. Advances in stationary phase technology could further improve selectivity and sensitivity for complex impurity profiles.

Conclusion

A robust reversed‐phase LC method using a C8 column and a carefully optimized gradient has been established to analyze perindopril tert‐butylamine, indapamide and nine impurities. The approach offers reliable separation, reproducible retention, and sensitive detection suitable for pharmaceutical quality control.

Reference

• Shimadzu Corporation ERAS‐1000‐0023 First Edition Mar 2023