Testing for Residual Solvent in Excipients

In the excipient production or R&D, organic solvents are often used to increase production or form expected crystal forms. Commonly used solvents include ethanol, acetone, and tetrahydrofuran, which are employed to optimize granulation, increase the dissolution rate, or disintegrate. While these organic volatile solvents have brought considerable output, quality, and profits to the industry, their negative impacts cannot be ignored. Scientifically strategies must be applied to control these incompletely removed solvents after processing. BOC Sciences' residual solvent testing service can help you ensure product quality and safety. We have developed and validated a range of in-house methods to test a number of commonly used solvents and have established rigorous analytical quality standards. Our technology is accurate enough to identify and quantify residual solvents present in samples, allowing manufacturers to trace problems back to specific steps in the manufacturing process.

Potential Risk of Residual Solvents

• Reduce the quality and safety of products
• Hazard to human health
• Pollute the environment
• Bring security risks to the production environment

Figure 1. Classification of Residual Solvents and Their Assessments. (Umamaheswari, D.; et al. 2021）

Testing Procedure

BOC Sciences has designed different residual solvent analysis methodologies for a variety of excipients. Our services help to ensure that the final drug product does not contain toxicologically significant levels of volatile organic compounds. Here is our standard testing workflow that can satisfy different testing program.

Information Needed for Testing

• Is the sample water-soluble or water-insoluble?
• List any known expected residual solvents
• Indicate whether you need a quantified data results
• Is a further release testing required?

Sampling Step

Headspace analysis is a commonly used technique to extract semi-volatile and volatile compounds. BOC Sciences mainly employs static headspace sampling method to analyze volatile organic compounds in excipients.

Separation Step

We offer a wide range of capillary columns to perform gas chromatographic (GC) separation step, specifically designed to identify different classes of residual solvents in the excipients.

• Procedure A - A G43 (6% cyanopropylphenyl-94% dimethylpolysiloxane) column is used to screen for and confirm the solvents’ presence
• Procedure B - A G16 (polyethylene glycol) column is applied to further confirm the solvents’ identity
• Procedure C - Either a G43 or G16 column is employed to quantify the amount of residual solvents

Detection Step

Recently, flame ionization detection (FID) has been recognized as a sensitive detector with good selectivity that can detect all carbon containing molecules. Therefore, at BOC Sciences, FID technique is used for trace analysis of organic solvents in excipients. We can identify the most commonly used solvents in the process, including:

• Acetone
• Butane
• Propane
• Pentane
• Hexane
• Heptane
• Ethanol
• Isopropanol

Figure 2. The Process of Determination of Residual Solvents. (Wenlong, Q.; et al. 2018)

Why Cooperate with BOC Sciences?

Discuss your testing needs with our team and we can develop a custom testing strategy for your project to ensure your final product complies with regulatory recommendations and current regulatory guidance.

• Scientific and regulatory expertise and resources
• Thorough understanding of methodologies and regulations
• Robust quality systems support
• Validation of analytical methods
• Comprehensive and accurate reporting
• Accurate and reliable data for accurate risk assessments