Residual Solvents Testing

Residual solvents testing is essential for identifying trace level chemical residues, formerly referred to as organic volatile impurities (OVIs), that are used in the manufacture of drug substances and excipients or in the preparation of drug products. These residues can also form as byproducts during the packaging and storage of pharmaceutical products, making accurate residual solvents testing critical for product safety, regulatory compliance, and overall drug quality.

The US pharmacopeia has set guidelines as to what amount of a particular solvent a person can be exposed to on a daily basis without developing complications due to overexposure. The types of solvents are divided into three classes. Class 1 organics should never be used. Class 2 organics are not recommended for use outside of a Good Manufacturing Practice (cGMP) environment where these substances are tightly controlled and continuously monitored due to their dangerous effects. Class 3 are solvents that present no known human health hazard at levels normally accepted in pharmaceuticals.

More importantly, chemical residues can have a significant impact on the health of a patient, especially over time and with repeated exposure. Your laboratory must ensure that patients are receiving the highest of quality, solvent-free drug product possible.

The implementation of United States Pharmacopeia (USP)<467> requires expertise that can provide extensive experience in optimizing gas chromatographic methods and analyzing volatile organic compounds in a variety of matrices in a timely manner, and our consulting services that we provide it as complimentary service in this regard.

Synergy Bioscience provides expert, rapid analysis support of all three classes of residual solvents. Our experienced team of scientists allow you to manage the large number of methods that may be involved in identification and quantification of impurities, including residual solvents.

Our Expertise Encompasses

  • Strict compliance with ICH guidelines
  • Detection, profiling, and control support of residual solvents in drug substances, excipients, and drug products
  • Water-soluble/insoluble raw materials and drug substance
  • Screening for potential interference
  • Screening for identification of unknown peaks
  • Feasibility studies
  • Validation of analytical methods
  • Comprehensive and accurate reports

Our Multiple Points of Interaction

  • Joint review of DMF/physicochemical properties of the API
  • Meetings to ensure appropriate:
    • Technology – GC-FID/TCD or GC/MS
    • Limits, e.g., TDI
    • Procedure for method transfer/validation
    • Process – prescreening, routine testing, API qualification

By testing for Residual Solvents, you will be able to ensure that your process is sound, using a high-quality solvent, free of impurities and toxic solvents,  and following proper manufacturing procedures (i.e. vacuum, desiccation, etc.). Utilizing a combination of Gas Chromatography with FID or TCD, Head-space analysis, and Mass Spectrometry, Synergy Bioscience Labs are able to identify all of the commonly used solvents and trace residues of chemicals in the process, such as:

  • Acetone
  • Butane
  • Propane
  • Pentane
  • Hexane
  • Heptane
  • Ethanol
  • Isopropanol (iso-alcohol), and many others

Synergy Bioscience offers a validated testing method to determine the amount of residual solvents introduced during processing of concentrates. By monitoring the ppm levels of solvents we will help identify raw materials and products that are free of harmful contamination.

  • We are currently testing for residual solvents using GC-FID coupled with headspace sampling which is the technique recommended by USP 467 for residual solvents in pharmaceuticals.
  • We have developed an in-house method that allows us to detect the light gases not included in USP 467.
  • We are currently testing for propane, isobutane, n-butane, isopentane, n-pentane, isopropanol, ethanol, acetone, hexane and naphtha all in one assay.

Standard Analysis

As part of a standard residual solvent analysis, we report all Class 1 and Class 2 solvents that are amenable to GC headspace analysis as defined in USP <467> and shown to work in practice.
Reasons for Choosing Synergy Bioscience

  • Expedited Turnaround Times Available
  • Standard Turn Around Time: 10 days
  • Accessible & Flexible
  • You will have one point of contact for seamless project management and our Quality Unit and Chemists are available upon request
  • Experienced
  • Synergy Bioscience has tested residual solvents since 1986; specifically performing method feasibility, development and validation for USP <467>
  • Validated
  • Our laboratory is cGMP compliance, FDA inspected/registered and DEA licensed.

Learn more about our pharmaceutical development services:
https://synergybioscience.com/pharmaceutical-development/