Residual solvents analysis using an Agilent Intuvo 9000 GC system

Význam tématu

Residual solvents represent potential impurities in pharmaceutical products that can affect safety, efficacy, and regulatory compliance. Accurate and efficient quantification of these solvents is mandated by USP <467> to ensure product quality and adherence to Good Manufacturing Practices. Modern analytical workflows benefit from methods that reduce analysis time, improve precision, and simplify laboratory operations.

Cíle a přehled studie

This work evaluates the performance of the Agilent Intuvo 9000 GC system coupled with the Agilent 7697A headspace sampler for USP <467> residual solvents analysis. By integrating an inlet splitter and dual flame ionization detectors (FIDs) with two distinct columns, the study aims to conduct both primary and confirmatory analyses in a single run, thereby cutting total runtime in half while maintaining or improving chromatographic reliability.

Použitá metodika a instrumentace

Sample Preparation:

• Three classes of residual solvent standards (Class 1, 2A, 2B) prepared via serial dilution in water.
• Headspace vials: 1 mL of standard dilution + 5 mL water.
• Nine replicates per solvent standard.

Instrumentation:

• Gas chromatograph: Agilent Intuvo 9000 GC with inlet splitter for dual FID detection.
• Headspace sampler: Agilent 7697A.
• Analytical columns: DB-624 Select Ultra Inert (30 m × 0.32 mm, 1.8 µm) and DB-WAX Ultra Inert (30 m × 0.32 mm, 0.25 µm).
• Carrier gas flow: constant 2 mL/min; detector gases: H₂ (30 mL/min), air (400 mL/min), N₂ make-up (25 mL/min).
• Temperature program: 40 °C hold, ramp at 15 °C/min to 180 °C, hold 3 min.
• Headspace conditions: vial oven & loop at 85 °C, transfer line at 100 °C, equilibration 40 min, injection 0.5 min, shake at 25 shakes/min.

Hlavní výsledky a diskuse

Retention Time and Area Repeatability:

• Retention time RSD ≤ 0.2 % for most analytes on both columns; some at < 0.1 %.
• Peak area RSD ≤ 5 % for all solvents; Class 2A exhibited best precision (≤ 2 %).

Chromatographic Resolution:

• DB-624 Select UI column provided superior separation of chlorinated solvents in Class 1.
• DB-WAX UI column improved separation of xylene isomers in Class 2A.
• Nitromethane peak shape and response markedly better on DB-WAX UI versus DB-624 UI.

Simultaneous Dual-Column Operation:

• Single-run analysis on both columns achieved full compliance with USP <467> confirmation requirements.
• Signal-to-noise for low-response analytes (e.g., carbon tetrachloride) met or exceeded acceptance criteria.

Přínosy a praktické využití metody

• Halved analysis time by eliminating separate runs for confirmation column.
• Maintained high reproducibility and low variability across multiple solvent classes.
• Simplified workflow with integrated headspace sampling and dual detection.
• Enhanced instrument uptime and throughput in QA/QC environments.

Budoucí trendy a možnosti využití

Integration of modular GC platforms with multiplexed detectors is expected to expand into other regulated analyses, such as pesticide residues and environmental volatiles. Advances in micro-flow and modular flow chips may further reduce carrier gas consumption and column conditioning times. Future developments could include automated method selection based on sample type and AI-driven data review to streamline regulatory submissions.

Závěr

The Agilent Intuvo 9000 GC combined with the 7697A headspace sampler and a dual-column, dual-FID configuration delivers robust, high-precision USP <467> residual solvent analysis in a single run. This approach offers excellent retention time and area repeatability, strong chromatographic resolution for diverse solvent classes, and significant time savings, making it an efficient solution for pharmaceutical quality control laboratories.

Reference

1. USP 40, General Chapter <467> Residual Solvents.
2. Firor RL. Analysis of USP <467> residual solvents… Agilent Technologies Application Note 5990-7625EN, 2012.
3. Tienport B, David F, Sandra P. Analysis of USP <467> residual solvents… Agilent Application Note 5991-1834EN, 2013.