Solvents - Analysis of impurities in pharmaceutical grade isopropanol

Importance of the topic

Ensuring the purity of pharmaceutical-grade isopropanol is critical for drug manufacturing and quality control. Impurities can compromise product safety, efficacy, and stability. A rapid, reliable analytical method is essential for routine monitoring, regulatory compliance, and minimizing batch rejection.

Objectives and overview of the study

This application note presents a fast gas chromatography method designed to separate and identify volatile impurities in 2-propanol. The primary goal is to achieve clear resolution of typical contaminants within a five-minute analysis time.

Methodology and instrumentation

• Technique: Gas chromatography with a wide-bore capillary column
• Column: Agilent CP-Select 624 CB fused silica WCOT, 30 m × 0.53 mm, film thickness 3.0 µm
• Temperature program: 50 °C initial, ramp at 10 °C/min to 200 °C
• Carrier gas: Nitrogen at 10 mL/min
• Injection: Direct injection of 0.02 µL sample at 250 °C
• Detection: Flame ionization detector at 250 °C
• Sample: Pharmaceutical-grade 2-propanol

Main results and discussion

The optimized method resolves 13 chromatographic peaks, including air, methanol, 2-propanol, 1-propanol, methyl ethyl ketone, 2-butanol, cyclohexane, n-butanol, methyl isobutyl ketone, 4-methyl-2-pentanol, mesityl oxide and two unknowns. All analytes elute within five minutes, with sharp peak shapes, good baseline stability, and reproducible retention times.

Benefits and practical applications

• Fast analysis reduces turnaround time and increases laboratory throughput
• Wide-bore column enhances sensitivity for trace-level impurities
• Direct injection simplifies sample preparation and lowers carryover risk
• Ideal for quality control of raw materials and finished products in pharmaceutical manufacturing

Future trends and possibilities for use

Future developments may include coupling GC with mass spectrometry for definitive compound identification, adoption of inert carrier gases to detect reactive impurities, miniaturized or portable GC systems for on-site testing, and green chromatography strategies to lower solvent use and environmental impact.

Conclusion

The presented GC-FID method using the Agilent CP-Select 624 CB column provides a rapid, reliable solution for monitoring volatile impurities in pharmaceutical-grade isopropanol, supporting efficient quality control and regulatory compliance.

Reference

• Agilent Technologies Application Note A01419, published October 31, 2011