Swab / Direct Combustion Carbon Analysis of Drug Residue by TOC-VCPH

Importance of Topic

The prevention of cross-contamination in pharmaceutical production is critical for product quality and patient safety. Cleaning validation ensures that residues from previously processed drugs or foreign materials do not compromise subsequent manufacturing.

Traditional methods such as HPLC require solvent extraction and extensive sample preparation, which can be time-consuming and complex. Total Organic Carbon (TOC) analysis combined with direct combustion offers a faster, simplified alternative that accommodates insoluble residues without additional pretreatment.

Study Objectives and Overview

This work demonstrates the use of the swab/direct combustion carbon analysis method employing Shimadzu's TOC-VCPH Analyzer and the SSM-5000A Solid Sample Combustion Unit to quantify drug residues. Representative drug substances (caffeine, acetaminophen, and tranexamic acid) were evaluated to assess measurement accuracy and recovery rates.

Sampling was performed by wiping known concentrations of drug solutions onto quartz silica fiber swabs, followed by direct combustion and carbon measurement without intermediate extraction steps.

Methodology and Instrumentation

• Sample Preparation: 100 µL of each 1000 mgC/L drug solution spread on a glass plate, dried, and collected using heat-treated quartz silica fiber filter paper.
• Combustion and Detection: Swabs placed in sample boats and directly combusted in the SSM-5000A unit; resulting CO₂ quantified by the TOC-VCPH Analyzer.
• Calibration: Generated from 30 µL of 1 % C glucose solution to establish the total carbon (TC) response curve.

Main Results and Discussion

• TC measurement values for caffeine, acetaminophen, and tranexamic acid closely matched theoretical concentrations, demonstrating high accuracy (949.6, 957.5, and 964.6 mgC/L, respectively, versus 1000 mgC/L target).
• Recovery tests on swab samples yielded rates above 95 % for all substances (97.1 % for caffeine, 100.2 % for acetaminophen, and 98.0 % for tranexamic acid), indicating reliable performance in practical sampling conditions.

Benefits and Practical Applications

The swab/direct combustion TOC approach offers several advantages:

• Eliminates solvent extraction and extensive pretreatment.
• Effectively measures both soluble and insoluble residues.
• Reduces analysis time and operator workload.
• Provides robust data for cleaning validation in pharmaceutical manufacturing.

Future Trends and Opportunities

Potential developments include:

• Automation of swab handling and sample introduction to increase throughput.
• Expansion to a wider range of pharmaceutical compounds and complex matrices.
• Integration with real-time monitoring systems for in-line cleaning validation.
• Combination with complementary detectors to distinguish organic classes.

Conclusion

The swab/direct combustion method using Shimadzu’s TOC-VCPH and SSM-5000A offers a streamlined, accurate, and versatile solution for quantifying drug residues in cleaning validation. Its ability to handle insoluble compounds and minimal sample preparation make it an attractive alternative to conventional HPLC-based protocols.

Instrumentation Used

• Shimadzu TOC-VCPH Total Organic Carbon Analyzer
• SSM-5000A Solid Sample Combustion Unit
• ADVANTEC QR-100 Quartz Silica Fiber Filter Paper (45 mm, heat-treated)