Appendix VIII M. Residual Ethylene Oxide and Dioxan

The test is intended for the determination of residual ethylene oxide and dioxan in samples soluble in water or dimethylacetamide. For substances that are insoluble or insufficiently soluble in these solvents, the preparation of the sample solution and the head-space conditions to be employed are given in the individual monograph.

Examine by head-space gas chromatography (2.2.28).

A. For samples soluble in or miscible with water, the following procedure may be used.

Test solution Weigh 1.00 g (M_T) of the substance to be examined in a 10 mL vial (other sizes may be used depending on the operating conditions) and add 1.0 mL of water R. Close and mix to obtain a homogeneous solution. Allow to stand at 70 °C for 45 min.

Reference solution (a) Weigh 1.00 g (M_R) of the substance to be examined into an identical 10 mL vial, add 0.50 mL of ethylene oxide solution R3 and 0.50 mL of dioxan solution R1. Close and mix to obtain a homogeneous solution. Allow to stand at 70 °C for 45 min.

Reference solution (b) To 0.50 mL of ethylene oxide solution R3 in a 10 mL vial add 0.1 mL of a freshly prepared 10 mg/L solution of acetaldehyde R and 0.1 mL of dioxan solution R1. Close and mix to obtain a homogeneous solution. Allow to stand at 70 °C for 45 min.

B. For samples soluble in or miscible with dimethylacetamide, the following procedure may be used.

Test solution Weigh 1.00 g (M_T) of the substance to be examined in a 10 mL vial (other sizes may be used depending on the operating conditions) and add 1.0 mL of dimethylacetamide R and 0.20 mL of water R. Close and mix to obtain a homogeneous solution. Allow to stand at 90 °C for 45 min.

Reference solution (a) Weigh 1.00 g (M_R) of the substance to be examined into a 10 mL vial, add 1.0 mL of dimethylacetamide R, 0.10 mL of dioxan solution R and 0.10 mL of ethylene oxide solution R2. Close and mix to obtain a homogeneous solution. Allow to stand at 90 °C for 45 min.

Reference solution (b) To 0.10 mL of ethylene oxide solution R2 in a 10 mL vial, add 0.1 mL of a freshly prepared 10 mg/L solution of acetaldehyde R and 0.10 mL of dioxan solution R. Close and mix to obtain a homogeneous solution. Allow to stand at 70 °C for 45 min.

The following static head-space injection conditions may be used:

• — equilibration temperature: 70 °C (90 °C for solutions in dimethylacetamide),

• — equilibration time: 45 min,

• — transfer-line temperature: 75 °C (150 °C for solutions in dimethylacetamide),

• — carrier gas: helium for chromatography R,

• — pressurisation time: 1 min,

• — injection time: 12 s.

The chromatographic procedure may be carried out using:

• — a capillary glass or quartz column 30 m long and 0.32 mm in internal diameter the inner surface of which is coated with a 1.0 µm thick layer of poly(dimethyl)siloxane R,

• — helium for chromatography R or nitrogen for chromatography R as the carrier gas with a linear velocity of about 20 cm/s and a split ratio of 1:20,

• — a flame-ionisation detector,

maintaining the temperature of the column at 50 °C for 5 min, then raising the temperature at a rate of 5 °C per minute to 180 °C and then raising the temperature at a rate of 30 °C per minute to 230 °C and maintaining at 230 °C for 5 min; maintaining the temperature of the injection port at 150 °C and that of the detector at 250 °C.

Inject a suitable volume, for example 1.0 mL, of the gaseous phase of reference solution (b). Adjust the sensitivity of the system so that the heights of the peaks due to ethylene oxide and acetaldehyde in the chromatogram obtained are at least 15 per cent of the full scale of the recorder. The test is not valid unless the resolution between the peaks corresponding to acetaldehyde and ethylene oxide is at least 2.0 and the peak of dioxan is detected with a signal-to-noise ratio of at least 5.

Inject separately suitable volumes, for example 1.0 mL (or the same volume used for reference solution (b)), of the gaseous phases of the test solution and reference solution (a). Repeat the procedure twice more.

For each pair of injections, calculate for ethylene oxide and for dioxan the difference in area between the peaks obtained with the test solution and reference solution (a). The test is not valid unless the relative standard deviation of the 3 values obtained for ethylene oxide is not greater than 15 per cent and the relative standard deviation of the 3 values obtained for dioxan is not greater than 10 per cent. If the weighings used for the test solution and reference solution differ from 1.00 g by more than 0.5 per cent, the appropriate corrections must be made.

The content of ethylene oxide or dioxan in parts per million is calculated from the expressions: