Diluent A— Prepare a mixture of nitric acid and water (1:1).

Diluent B— Prepare a mixture of nitric acid and hydrochloric acid (9:1).

Standard solutions— Transfer about 0.1 mL (234 mg) of antimony pentachloride, accurately weighed, to a 50-mL volumetric flask, dilute with Diluent B to volume, and mix. This stock solution contains about 1906 µg of antimony per mL. Dilute a portion of this solution quantitatively and stepwise with Diluent B to obtain Standard solutions containing 2.5, 5.0, and 10.0 µg of antimony per mL.

Test solution— Accurately weigh a stoppered stock bottle containing a quantity of Desflurane at ambient temperature, and then cool it in powdered dry ice. Using a cold syringe, transfer between 5 and 7 mL of Desflurane from the cold bottle to a separator containing 20 mL of Diluent A. Allow the stock bottle containing the remaining Desflurane to come to ambient temperature, weigh it accurately, and calculate the quantity, in g, of Desflurane taken for the test. Allow the Desflurane in the separator to evaporate, and with the aid of a few mL of Diluent A transfer the acid solution to a clean, dry beaker. Add 1 mL of hydrochloric acid to the solution in the beaker, and reduce the volume to about 8 mL by evaporating on a hot plate. Transfer this solution to a 10-mL volumetric flask, dilute with Diluent B to volume, and mix.

Procedure— Concomitantly determine the absorbances of the Standard solutions and the Test solution at the antimony emission line at 217.6 nm with an atomic absorption spectrophotometer (see Spectrophotometry and Light-scattering 851) equipped with an antimony hollow-cathode lamp and an air–acetylene flame, using Diluent B as the blank. Plot the absorbances of the Standard solutions versus concentration, in µg per mL, of antimony, and draw the straight line best fitting the three plotted points. From the graph so obtained, determine the concentration, C, in µg per mL, of antimony in the Test solution. Calculate the quantity, in ppm, of antimony in the portion of Desflurane taken by the formula: in which W is the quantity, in g, of Desflurane taken to prepare the Test solution. Not more than 3 µg per g is found.

Buffer solution— Dissolve 57 mL of glacial acetic acid, 58 g of sodium chloride, and 4 g of (1,2-cyclohexylenedinitrilo)tetraacetic acid in 500 mL of water. Adjust with 5 N sodium hydroxide to a pH of 5.25 ± 0.25, dilute with water to 1000 mL, and mix.

Standard solutions— Quantitatively dissolve an accurately weighed quantity of USP Sodium Fluoride RS in water to obtain a solution containing 2210 µg per mL. Each mL of this solution contains 1000 µg of fluoride per mL. Dilute accurately measured volumes of this stock solution with Buffer solution to obtain solutions having concentrations of 0.1, 0.3, 0.5, 1.0, 3.0, and 5.0 µg of fluoride per mL.

Test solution— Transfer 10.0 mL of Desflurane to a 60-mL separator, add 10.0 mL of water, shake for 1 minute, and allow the layers to separate. Drain the lower organic layer and a small portion of the aqueous layer into a beaker, and discard. Transfer 5.0 mL of the aqueous phase remaining in the separator to a plastic cup, add 5.0 mL of Buffer solution, and mix. [NOTE—Transfer the aqueous phase remaining in the separator to a second plastic cup, and reserve for the pH determination.]

Procedure— Concomitantly measure the potentials (see pH 791), in mV, of the Standard solutions and the Test solution with a pH meter capable of a minimum reproducibility of ±0.2 mV and equipped with a fluoride-specific ion-indicating electrode and a calomel reference electrode. [NOTE—When taking measurements, immerse the electrodes in the solution, stir with a polytef-coated stirring bar and a magnetic stirrer having an insulated top until equilibrium is attained (about 1 to 2 minutes), and record the potential. Rinse the electrodes with Buffer solution, and dry, taking care to avoid damaging the crystal of the specific-ion electrode.] Plot the logarithms of the fluoride concentrations, in µg per mL, of the Standard solutions versus potential, in mV. From the measured potential of the Test solution and the standard response line, determine the concentration, C, in µg per mL, of fluoride in the Test solution. Multiply C by 0.0002 to obtain the percentage of fluoride in the Desflurane taken. Not more than 0.001% is found.

Standard solution— Insert a rubber-sleeve stopper into a 2-mL vial, weigh accurately, and partially evacuate the vial. Using a cold syringe, inject about 680 µL of USP Desflurane RS, previously cooled to 0 to 5, into the vial. Allow the vial to come to ambient temperature, accurately weigh it, and calculate the quantity, in mg, of USP Desflurane RS added. Using a syringe, inject about 7 µL of USP Desflurane Related Compound A RS into the same vial, accurately weigh, and calculate the quantity, in mg, of USP Desflurane Related Compound A RS added. Similarly, and in turn, add about 7.2 µL of trichlorofluoromethane, 7.4 µL of dichlorofluoromethane, 7.6 µL of methylene chloride, 6.8 µL of chloroform, 6.3 µL of trichlorotrifluoroethane, and 6.7 µL of isoflurane, accurately weighing the vial after each addition, and calculating the quantity, in mg, of each addition. Calculate the percentage, PS, of each impurity in the Standard solution taken by the formula: in which Wi is the quantity, in mg, of the respective impurity added during the preparation of the Standard solution; WD is the quantity, in mg, of USP Desflurane RS in the Standard solution; and Wt is the sum of all the impurities added during the preparation of the Standard solution.

Test solution— Use Desflurane.

Chromatographic system (see Chromatography 621)— The gas chromatograph is equipped with a flame-ionization detector and a 2.4-mm × 6.1-m stainless steel column packed with 25% phase G16 on 80- to 100-mesh support S1A. Helium is used as the carrier gas at a flow rate of about 20 mL per minute. The column temperature is maintained at about 75, the injection port temperature at about 200, and the detector temperature at about 250. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for trichlorofluoromethane, 0.86 for bis-(1,2,2,2-tetrafluoroethyl)ether (desflurane related compound A), 1.0 for desflurane, 1.7 for dichlorofluoromethane, 2.6 for isoflurane, 3.7 for methylene chloride, and 6.6 for chloroform; the resolution, R, between trichlorofluoromethane and desflurane related compound A is not less than 1.2; and the tailing factor for the desflurane related compound A peak is not more than 1.5.

Procedure— Separately inject 1 µL of the Standard solution and 2 µL of the Test solution into the chromatograph, record the chromatograms for 40 minutes, and measure the area responses for all the peaks. Calculate the percentage of each impurity taken by the formula: in which PS is the percentage of the respective impurity in the Standard solution; ri is the peak response of the respective impurity in the chromatogram obtained from the Test solution; and rS is the response of the respective impurity peak in the chromatogram obtained from the Standard solution. Not more than 1.0% of isoflurane, 0.1% of methylene chloride, 0.1% of desflurane related compound A, 0.05% of chloroform, 0.025% of trichlorotrifluoroethane, 0.01% of dichlorofluoromethane, and 0.01% of trichlorofluoromethane are found.

(Official January 1, 2007)

Internal standard solution— Dilute an accurately measured volume of USP Halothane RS with p-xylene, and dilute quantitatively, and stepwise if necessary, with p-xylene to obtain a solution having a known concentration of about 20 µL per mL.

Standard preparation— Transfer 1.0 mL of Internal standard solution to a 2.0-mL septum-capped vial, cap, seal, and weigh accurately. Using a cold syringe, inject about 25 µL of USP Desflurane RS, previously cooled to 0 to 5, into the vial. Allow the vial to come to ambient temperature, accurately weigh it, and calculate the quantity, in mg, of USP Desflurane RS added.

Assay preparation— Transfer 1.0 mL of Internal standard solution to a 2.0-mL septum-capped vial, cap, seal, and weigh accurately. Using a cold syringe, inject about 25 µL of Desflurane, previously cooled to 0 to 5, into the vial. Allow the vial to come to ambient temperature, accurately weigh it, and calculate the quantity, in mg, of Desflurane added.

Chromatographic system (see Chromatography 621)— The gas chromatograph is equipped with a flame-ionization detector and a 2.4-mm × 3.7-m stainless steel column coated with polytef and packed with 10% phase G31 and 15% phase G18 on 80- to 100-mesh support S1A. Helium is used as the carrier gas at a flow rate of about 24 mL per minute. The chromatograph is programmed as follows. Initially the temperature of the column is maintained at about 80 for 2.5 minutes, then increased at a rate of 2 per minute, to 88, maintained at 88 for 3 minutes, then increased to 175 at a rate of 70 per minute, and maintained at 175 for 4 minutes. The injection port temperature is maintained at about 200, and the detector temperature at about 250. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are 1.0 for desflurane and about 2.8 for halothane; the resolution, R, between desflurane and halothane is not less than 8; and the relative standard deviation for the ratios of the desflurane peak response to the halothane peak response obtained for replicate injections is not more than 1.0%.

Procedure— Separately inject equal volumes (about 1 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak area responses for the halothane and desflurane peaks. Calculate the percentage of C3H2F6O in the Desflurane taken by the formula: in which WS is the quantity, in mg, of USP Desflurane RS used to prepare the Standard preparation; WU is the quantity, in mg, of Desflurane used to prepare the Assay preparation; and RU and RS are the ratios of the peak area responses of desflurane to that of halothane obtained from the Assay preparation and the Standard preparation, respectively.