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6.5 DETERMINATION OF ETHANOL

Method I Distillation Method​

      Method I is to be used for the determination of ethanol, unless otherwise specified in the individual monograph. It is suitable for examining liquid pharmaceutical preparation such as fluid extracts and tinctures, provided the capacity of the distilling flask is sufficient (commonly two to four times the volume of the liquid to be heated) and the rate of distillation is such that clear distillates are produced. Cloudy distillates may be clarified by agitation with talc, or with calcium carbonate, and filtered, after which the temperature of the filtrate is adjusted and the ethanol content determined from the specific gravity. During all manipulations, take precautions to minimize the loss of ethanol by evaporation.

      Apparatus The apparatus (see Figure) consists of a round-bottomed flask (A) fitted with a distillation head (B) with a steam trap and attached to a vertical condenser (C). The latter is fitted at its lower part with a tube (D) which carries the distillate into the lower part of a 100-ml or 250-ml volumetric flask. The volumetric flask is immersed in a mixture of ice and water (E) during the distillation. A disc having a circular aperture 6 cm in diameter is placed under flask (A) to reduce the risk of charring of any dissolved substances.

      FROTHING Treat liquids that froth to a troublesome extent during distillation by rendering them strongly acid with phosphoric, sulfuric, or tannic acid, or treat with a slight excess of calcium chloride solution, or with a small amount of paraffin or silicone oil before starting the distillation.

      BUMPING Prevent bumping during distillation by adding porous chips of insoluble material such as silicon carbide, or beads.

Apparatus for the Determination of Ethanol Content Dimensions in mm

      For liquids presumed to contain 30 per cent of ethanol or less By means of a pipette, transfer to a suitable distilling apparatus not less than 25 ml of the liquid in which the ethanol is to be determined, and note the temperature at which the volume was measured. Add an equal volume of water, distil, and collect a volume of distillate about 2 ml less than the volume taken of the original test liquid. Adjust to the temperature at which the original test liquid was measured, add sufficient water to measure exactly the original volume of the test liquid, and mix. The distillate is clear or not more than slightly cloudy, and does not contain more than traces of volatile substances other than ethanol and water. Determine the specific gravity of the liquid at 25º (Appendix 4.9), using this result to ascertain the percentage, by volume, of C₂H₅OH contained in the liquid examined by reference to the Alcoholometric Table, p. 496.

      For liquids presumed to contain more than 30 per cent of ethanol Proceed as directed in the foregoing paragraph, except: dilute the specimen with about twice its volume of water, and collect a volume of distillate about 2 ml less than twice the volume of the original test liquid. Bring to the temperature at which the original liquid was measured, add sufficient water to measure exactly twice the original volume of the test liquid, mix, and determine its specific gravity. The proportion of C₂H₅OH by volume, in this distillate, as ascertained from its specific gravity, equals one-half that in the liquid examined.

      Special Treatment

      VOLATILE ACIDS AND BASES Render preparations containing volatile bases slightly acidic with dilute sulfuric acid before distilling. If volatile acids are present, render the preparation slightly alkaline with sodium hydroxide TS.

      GLYCEROL To liquids that contain glycerol add sufficient water so that the residue, after distillation, contains not less than 50 per cent of water. 

      IODINE Treat all solutions containing free iodine with zinc powder before the distillation, or decolorize with just sufficient 10 per cent w/v solution of sodium thiosulfate, followed by a few drops of sodium hydroxide TS.

      OTHER VOLATILE SUBSTANCES Spirits, elixirs, tinctures, and similar preparations that contain appreciable proportions of volatile materials other than ethanol and water, such as volatile oils, chloroform, ether, camphor, etc., require special treatment, as follows:

      For liquids presumed to contain 50 per cent of ethanol or less Mix 25 ml of the sample under examination, accurately measured, with about an equal volume of water in a separator. Saturate this mixture with sodium chloride, then add 25 ml of petroleum ether (boiling range, 40º to 60º), and shake the mixture to extract the interfering volatile ingredients. Draw off the separated, lower layer into a second separator, and repeat the extraction twice with two further 25-ml portions of petroleum ether (boiling range, 40º to 60º). Extract the combined petroleum ether solutions with three 10-ml portions of a saturated solution of sodium chloride. Combine the saline solutions, and distil in the usual manner, collecting a volume of distillate having a simple ratio to the volume of the original sample.

      For liquids presumed to contain more than 50 per cent of ethanol Adjust the sample under examination to a concentration of approximately 25 per cent of ethanol by diluting it with water. Then proceed as directed in the preceding paragraph, beginning with “Saturate this mixture with sodium chloride...”.

      In preparing Collodion or Flexible Collodion for distillation, use water in place of the saturated solution of sodium chloride directed above.

      If volatile oils are present in small proportions only and a cloudy distillate is obtained, the petroleum ether treatment not having been employed, the distillate may be clarified and rendered suitable for the specific gravity determination by shaking it with about one-fifth its volume of petroleum ether (boiling range, 40º to 60º), or by filtering it through a thin layer of talc.

Method II Gas Chromatographic Method

      Method II is to be used where specified in the individual monograph.

      Carry out the determination as described in the “Gas Chromatography” (Appendix 3.4).

      Standard preparation Dilute 5.0 ml of absolute ethanol and 5.0 ml of 1-propanol with water to produce 100.0 ml.

      Assay preparation Prepare the following two solutions.

      SOLUTION (A) Dilute a volume of the preparation being examined with water to obtain a solution containing between 4.0 and 6.0 per cent v/v of ethanol.

      SOLUTION (B) Dilute a volume of the preparation being examined and a volume of 1-propanol with water to obtain a solution containing between 4.0 and 6.0 per cent v/v of ethanol and 5.0 per cent v/v of 1-propanol.

      Chromatographic system The chromatographic procedure may be carried out using (a) a glass column (1.5 m × 4 mm) packed with porous polymer beads (100 to 120 mesh), maintained at 150º (either Porapak Q or Chromosorb 101 is suitable), (b) nitrogen as the carrier gas, and (c) a flame ionization detector; maintain the injection port and the detector at 170º.

      System suitability In a suitable chromatogram, the resolution factor is not less than 2, the symmetry factor of the ethanol peak is not more than 2.0, and six replicate injections of the Standard preparation show a relative standard deviation of not more than 2.0 per cent in the ratio of the peak of ethanol to the peak of 1-propanol.

      Calculation Calculate the content of C₂H₅OH from the peak areas or peak heights obtained.

ALCOHOLOMETRIC TABLE

Based upon data appearing in Bull. Natl. Bur. Std., 1913, 9(3), 424-425.

ALCOHOLOMETRIC TABLE (continued)

Based upon data appearing in Bull. Natl. Bur. Std., 1913, 9(3), 424-425.

ALCOHOLOMETRIC TABLE (continued)

Based upon data appearing in Bull. Natl. Bur. Std., 1913, 9(3), 424-425.