USP35-ROI和重金属检查方法

USP35 重金属检查和灼烧残渣方法

231 HEAVY METALS (重点看Method Ⅱ)

This test is provided to demonstrate that the content of metallic impurities that are colored by sulfide ion, under the specified test conditions, does not exceed the Heavy metals limit specified in the individual monograph in terms of the percentage (by weight)of lead in the test substance, as determined by concomitant visual comparison (see Visual Comparison in the section Procedure under Spectrophotometry and Light-Scattering <851>)with a control prepared from a Standard Lead Solution.[NOTE—Substances that typically will respond to this test are lead,mercury,bismuth,arsenic,antimony,tin,cadmium,silver,copper,and molybdenum.] Determine the amount of heavy metals by Method I, unless otherwise specified in the individual monograph. Method I is used for substances that yield clear, colorless preparations under the specified test conditions. Method II is used for substances that do not yield clear, colorless preparations under the test conditions specified for Method I, or for substances that, by virtue of their complex nature, interfere with the precipitation of metals by sulfide ion, or for fixed and volatile oils. Method III, a wet-digestion method, is used only in those cases where neither Method I nor Method II can be utilized.

Special Reagents

Lead Nitrate Stock Solution— Dissolve 159.8mg of lead nitrate in 100mLof water to which has been added 1mLof nitric acid, then dilute with water to 1000mL.Prepare and store this solution in glass containers free from soluble lead salts.

Standard Lead Solution— On the day of use, dilute 10.0mLof Lead Nitrate Stock Solution with water to 100.0mL.Each m L of Standard Lead Solution contains the equivalent of 10µg of lead. A comparison solution prepared on the basis of 100µLof Standard Lead Solution per g of substance being tested contains the equivalent of 1part of lead per million parts of substance being tested.

Method I

pH3.5 Acetate Buffer— Dissolve 25.0 g of ammonium acetate in 25mL of water, and add 38.0mLof 6N hydrochloric acid. Adjust, if necessary, with 6N ammonium hydroxide or 6N hydrochloric acid to a pH of 3.5, dilute with water to 100mL, and mix.

Standard Preparation— Into a 50-mLcolor-comparison tube pipet 2mL of Standard Lead Solution(20µg of Pb ),and dilute with water to 25mL.Adjust with 1N acetic acid or 6N ammonium hydroxide to a pH between 3.0and 4.0,using short-range pH indicator paper as external indicator, dilute with water to 40mL,and mix.

Test Preparation— Into a 50-mLcolor-comparison tube place 25mLof the solution prepared for the test as directed in the individual monograph; or, using the designated volume of acid where specified in the individual monograph, dissolve in and dilute with water to 25mLthe quantity, in g, of the substance to be tested, as calculated by

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the formula: 2.0/(1000L),

in which L is the Heavy metals limit, in percentage. Adjust with 1N acetic acid or 6N ammonium hydroxide to a pH between 3.0 and 4.0, using short-range pH indicator paper as external indicator, dilute with water to 40mL, and mix.

Monitor Preparation— Into a third 50-mLcolor-comparison tube place 25mLof a solution prepared as directed for Test Preparation, and add 2.0mLof Standard Lead Solution. Adjust with 1N acetic acid or 6N ammonium hydroxide to a pH between 3.0and 4.0, using short-range pH indicator paper as external indicator, dilute with water to 40mL, and mix.

Procedure— To each of the three tubes containing the Standard Preparation, the Test Preparation, and the Monitor Preparation, add 2mLof pH3.5Acetate Buffer, then add 1.2mLof thioacetamide–glycerin base TS, dilute with water to 50mL,mix,allow to stand for 2minutes,and view downward over a white surface *:the color of the solution from the Test Preparation is not darker than that of the solution from the Standard Preparation, and the intensity of the color of the Monitor Preparation is equal to or greater than that of the Standard Preparation.[NOTE—If the color of the Monitor Preparation is lighter than that of the Standard Preparation, use Method II instead of Method I for the substance being tested.]

Method II

pH 3.5 Acetate Buffer— Prepare as directed under Method I. Standard Preparation— Prepare as directed under Method I.

Test Preparation— Use a quantity, in g, of the substance to be tested as calculated by the formula: 2.0/(1000L),

in which L is the Heavy metals limit, in percentage. Transfer the weighed quantity of the substance to a suitable crucible, add sufficient sulfuric acid to wet the substance, and carefully ignite at a low temperature until thoroughly charred. (The crucible may be loosely covered with a suitable lid during the charring.) Add to the carbonized mass 2mLof nitric acid and 5drops of sulfuric acid, and heat cautiously until white fumes no longer are evolved. Ignite, preferably in a muffle furnace, at 500℃ to 600℃, until the carbon is completely burned off. Cool, add 4mLof 6N hydrochloric acid, cover, digest on a steam bath for 15minutes, uncover, and slowly evaporate on a steam bath to dryness. Moisten the residue with 1drop of hydrochloric acid, add 10mLof hot water, and digest for 2minutes.Add 6N ammonium hydroxide dropwise, until the solution is just alkaline to litmus paper, dilute with water to 25mL,and adjust with 1Nacetic acid to a pH between 3.0 and 4.0,using short-range pH indicator paper as external indicator. Filter if necessary, rinse the crucible and the filter with 10mLof water, combine the filtrate and rinsing in a 50-mLcolor-comparison tube, dilute with water to 40mL, and mix.

Procedure— To each of the tubes containing the Standard Preparation and the Test Preparation, add 2mLof pH3.5 Acetate Buffer, then add 1.2mLof thioacetamide–glycerin base TS, dilute with water to 50mL, mix,allow to stand for

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2minutes,and view downward over a white surface*:the color of the solution from the Test Preparation is not darker than that of the solution from the Standard Preparation. Method III

pH3.5 Acetate Buffer— Prepare as directed under Method I.

Standard Preparation— Transfer a mixture of 8mLof sulfuric acid and 10mLof nitric acid to a clean,dry,100-mL Kjeldahl flask, and add a further volume of nitric acid equal to the incremental volume of nitric acid added to the Test Preparation. Heat the solution to the production of dense, white fumes, cool, cautiously add 10mLof water and, if hydrogen peroxide was used in treating the Test Preparation, add a volume of 30percent hydrogen peroxide equal to that used for the substance being tested, and boil gently to the production of dense, white fumes. Again cool, cautiously add 5mLof water, mix, and boil gently to the production of dense, white fumes and to a volume of 2-3mL.Cool, dilute cautiously with a few mL of water, add 2.0mLof Standard Lead Solution(20µg of Pb),and mix. Transfer to a 50-mLcolor-comparison tube, rinse the flask with water, adding the rinsing to the tube until the volume is 25mL, and mix. Test Preparation—

If the substance is a solid— Transfer the quantity of the test substance specified in the individual monograph to a clean, dry, 100-mL Kjeldahl flask. [NOTE—A300-mLflask may be used if the reaction foams excessively.]Clamp the flask at an angle of 45 , and add a sufficient quantity of a mixture of 8mLof sulfuric acid and 10mLof nitric acid to moisten the substance thoroughly. Warm gently until the reaction commences, allow the reaction to subside, and add additional portions of the same acid mixture, heating after each addition, until a total of 18mLof the acid mixture has been added. Increase the amount of heat, and boil gently until the solution darkens. Cool, add 2mLof nitric acid, and heat again until the solution darkens. Continue the heating, followed by addition of nitric acid until no further darkening occurs, then heat strongly to the production of dense, white fumes. Cool, cautiously add 5mLof water, boil gently to the production of dense, white fumes, and continue heating until the volume is reduced to a few mL. Cool, cautiously add 5mLof water, and examine the color of the solution. If the color is yellow, cautiously add 1mLof 30percent hydrogen peroxide, and again evaporate to the production of dense, white fumes and a volume of 2- 3mL.If the solution is still yellow in color, repeat the addition of 5mLof water and the peroxide treatment. Cool, dilute cautiously with a few mL of water, and rinse into a 50-mLcolor-comparison tube, taking care that the combined volume does not exceed 25mL.

If the substance is a liquid— Transfer the quantity of the test substance specified in the individual monograph to a clean, dry, 100-mL Kjeldahl flask.[NOTE—A300-mLflask may be used if the reaction foams excessively.]Clamp the flask at an angle of 45, and cautiously add a few mL of a mixture of 8mLof sulfuric acid and 10mLof nitric acid. Warm gently until the reaction commences, allow the reaction to subside, and proceed as directed under If the substance is a solid, beginning with “add additional portions of the same acid mixture.”

Procedure— Treat the Test Preparation and the Standard Preparation as follows: Adjust the solution to a pH between 3.0and 4.0, using short-range pH indicator paper

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as external indicator, with ammonium hydroxide (a dilute ammonia solution may be used, if desired, as the specified range is approached), dilute with water to 40mL, and mix.

To each tube add 2mL of pH3.5 Acetate Buffer, then add 1.2mL of thioacetamide-glycerin base TS, dilute with water to 50mL,mix, allow to stand for 2minutes, and view downward over a white surface*:the color of the Test Preparation is not darker than that of the Standard Preparation.

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