Residual Solvents

METHOD

SOP C.26.1.

Almost any solvent used in peptide synthesis can be quantified by this method. Contrasting the usually applied head space analysis, we employ a direct approach where a solution is injected in a split injection and subjected to capillary gas chromatography. This procedure closely follows the USP guideline 467 for the determination of Organic Volatile Impurities (OVI).

A contemporary list of all routinely determined OVIs is available. Please contact us for the list of solvents. 

OVIs which are currently not implemented in our standard routine could be incorporated by three point calibration upon customer request.

OVI detection is routinely performed in four modalities:

Targeted determination

In our targeted approach, a known OVI is detected and quantified. An analysis in duplicate is usually carried out in order to probe for sample homogeneity. Critical solvents like bases or solvents with higher retention times require an enhanced SST of the instrument.

Spiking Experiment

Some solvents, especially basic ones, could be discriminated by the sample matrix. This could lead to inconsistent recovery rates which do not reflect the actual amount of solvent present in the sample. To test for such influences, a substance specific validation is recommended. During validation, the solvent discrimination is evaluated by spiking known amounts of solvent and measuring the recovery.

 Screening experiment

Testing for the presence of unknown solvents is performed in an untargeted screening approach. We offer two panels for screening, depending on the number of solvents which should be tested for. 

„Regular“: Includes all solvents which are marked in column SCR1. The standard LOQ is reported.

„Expanded“: Includes all solvents which are listed in column SCR2. Standard LOQ is reported. An expanded screening contains all standard solvents as well as solvents which demand for a bespoke sample preparation.

Identity of solvents

To identify a solvent, traces of the solvent are directly injected and analysed by GC-FID. Identification is performed by retention time comparison with a traceable standard (if available).

SPECIFICATIONS

  • generic validation
  • specifications are solvent dependent and can be found in our OVI-List.

REPORTED RESULTS

  • content of solvent in [ppm]
  • LOD
  • LOQ

SAMPLE REQUIREMENTS

  • samples with low boiling solvents should be shipped under temperature control
  • use tightly sealable sample vials (e.g. with crimp top) to prevent premature solvent evaporation
  • 3 mg (single analysis), 5 mg (duplicate analysis)
  • 5 mg of sample for screening experiments
  • 1 ml for solvent identification. Smaller volumes (>100 µl) are possible, if the sample vessel is properly sealed.
  • please note: larger sample quantities are advantageous for sample handling and reduction of evaporation prior to analysis. We recommend to send about 10 mg of sample in a small vessel which can be tightly sealed (e.g. crimp top)

ADDITIONAL SERVICES

  • determination of blind values
  • reporting of reduced LOQ (only applies to specific solvents)
  • method development for solvents which are currently not listed on our OVI-List. This includes a three point calibration and estimation of LOQ and LOD.
  • additional injections of 6x SST which could be required for submissions
  • Please contact us for a substance specific validation
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