美國藥典34重金屬231中英文.doc

231 HEAVY METALSThis 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 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. noteSubstances 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 used.Special Reagents Lead Nitrate Stock Solution Dissolve 159.8 mg of lead nitrate in 100 mL of water to which has been added 1 mL of nitric acid, then dilute with water to 1000 mL. Prepare and store this solution in glass containers free from soluble lead salts. Standard Lead Solution On the day of use, dilute 10.0 mL of Lead Nitrate Stock Solution with water to 100.0 mL. Each mL of Standard Lead Solution contains the equivalent of 10 g of lead. A comparison solution prepared on the basis of 100 L of Standard Lead Solution per g of substance being tested contains the equivalent of 1 part of lead per million parts of substance being tested. Method I pH 3.5 Acetate Buffer Dissolve 25.0 g of ammonium acetate in 25 mL of water, and add 38.0 mL of 6 N hydrochloric acid. Adjust, if necessary, with 6 N ammonium hydroxide or 6 N hydrochloric acid to a pH of 3.5, dilute with water to 100 mL, and mix. Standard Preparation Into a 50-mL color-comparison tube pipet 2 mL of Standard Lead Solution (20 g of Pb), and dilute with water to 25 mL. Using a pH meter or short-range pH indicator paper as external indicator, adjust with 1 N acetic acid or 6 N ammonium hydroxide to a pH between 3.0 and 4.0, dilute with water to 40 mL, and mix. Test Preparation Into a 50-mL color-comparison tube place 25 mL of 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 25 mL the 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, as a percentage. Using a pH meter or short-range pH indicator paper as external indicator, adjust with 1 N acetic acid or 6 N ammonium hydroxide to a pH between 3.0 and 4.0, dilute with water to 40 mL, and mix. Monitor Preparation Into a third 50-mL color-comparison tube place 25 mL of a solution prepared as directed for Test Preparation, and add 2.0 mL of Standard Lead Solution. Using a pH meter or short-range pH indicator paper as external indicator, adjust with 1 N acetic acid or 6 N ammonium hydroxide to a pH between 3.0 and 4.0, dilute with water to 40 mL, and mix. Procedure To each of the three tubes containing the Standard Preparation, the Test Preparation, and the Monitor Preparation, add 2 mL of pH 3.5 Acetate Buffer, then add 1.2 mL of thioacetamideglycerin base TS, dilute with water to 50 mL, mix, allow to stand for 2 minutes, 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 color of the solution from the Monitor Preparation is equal to or darker than that of the solution from the Standard Preparation. noteIf 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 noteThis method does not recover mercury. 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 2 mL of nitric acid and 5 drops 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 4 mL of 6 N hydrochloric acid, cover, digest on a steam bath for 15 minutes, uncover, and slowly evaporate on a steam bath to dryness. Moisten the residue with 1 drop of hydrochloric acid, add 10 mL of hot water, and digest for 2 minutes. Add 6 N ammonium hydroxide dropwise until the solution is just alkaline to litmus paper, dilute with water to 25 mL, and adjust with 1 N acetic acid to a pH between 3.0 and 4.0, using short-range pH indicator paper as an external indicator. Filter if necessary, rinse the crucible and the filter with 10 mL of water, combine the filtrate and rinsing in a 50-mL color-comparison tube, dilute with water to 40 mL, and mix. Procedure To each of the tubes containing the Standard Preparation and the Test Preparation, add 2 mL of pH 3.5 Acetate Buffer, then add 1.2 mL of thioacetamideglycerin base TS, dilute with water to 50 mL, mix, allow to stand for 2 minutes, 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 pH 3.5 Acetate Buffer Prepare as directed under Method I. Standard Preparation Transfer a mixture of 8 mL of sulfuric acid and 10 mL of 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 10 mL of water; and, if hydrogen peroxide was used in treating the Test Preparation, add a volume of 30 percent hydrogen peroxide equal to that used for the substance being tested. Boil gently to the production of dense, white fumes. Again cool, cautiously add 5 mL of water, mix, and boil gently to the production of dense, white fumes and to a volume of 2 to 3 mL. Cool, dilute cautiously with a few mL of water, add 2.0 mL of Standard Lead Solution (20 g of Pb), and mix. Transfer to a 50-mL color-comparison tube, rinse the flask with water, adding the rinsing to the tube until the volume is 25 mL, and mix. Test Preparation Unless otherwise indicated in the individual monograph, 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, as a percentage. If the substance is a solid Transfer the weighed quantity of the test substance to a clean, dry, 100-mL Kjeldahl flask. noteA 300-mL flask 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 8 mL of sulfuric acid and 10 mL of nitric acid to moisten the substance thoroughly. Warm gently until the reaction commences, allow the reaction to subside, and add portions of the same acid mixture, heating after each addition, until a total of 18 mL of the acid mixture has been added. Increase the amount of heat, and boil gently until the solution darkens. Cool, add 2 mL of 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 5 mL of 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 5 mL of water, and examine the color of the solution. If the color is yellow, cautiously add 1 mL of 30 percent hydrogen peroxide, and again evaporate to the production of dense, white fumes and a volume of 2 to 3 mL. If the solution is still yellow, repeat the addition of 5 mL of water and the peroxide treatment. Cool, dilute cautiously with a few mL of water, and rinse into a 50-mL color-comparison tube, taking care that the combined volume does not exceed 25 mL. If the substance is a liquid Transfer the weighed quantity of the test substance to a clean, dry, 100-mL Kjeldahl flask. noteA 300-mL flask 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 8 mL of sulfuric acid and 10 mL of nitric acid. Warm gently until the reaction commences, allow the reaction to subside, and proceed as directed for If the substance is a solid, beginning with “add portions of the same acid mixture.” Monitor Preparation Proceed with the digestion, using the same amount of sample and the same procedure as directed in the subsection If the substance is a solid in the section Test Preparation, until the step “Cool, dilute cautiously with a few mL of water.” Add 2.0 mL of Lead Standard Solution (20 g of lead), and mix. Transfer to a 50-mL color comparison tube, rinse the flask with water, adding the rinsing to the tube until the volume is 25 mL, and mix. Procedure Treat the Test Preparation, the Standard Preparation, and the Monitor Preparation as follows. Using a pH meter or short-range pH indicator paper as external indicator, adjust the solution to a pH between 3.0 and 4.0 with ammonium hydroxide (a dilute ammonia solution may be used, if desired, as the specified range is approached), dilute with water to 40 mL, and mix. To each tube add 2 mL of pH 3.5 Acetate Buffer, then add 1.2 mL of thioacetamideglycerin base TS, dilute with water to 50 mL, mix, allow to stand for 2 minutes, and view downward over a white surface*: the color of the Test Preparation is not darker than that of the Standard Preparation, and the color of the Monitor Preparation is equal to or darker than that of the Standard Preparation. * In those countries or jurisdictions where thioacetamide cannot be used, add 10 mL of freshly prepared hydrogen sulfide TS to each of the tubes, mix, allow to stand for 5 minutes, and view downward over a white surface. Auxiliary Information Please check for your question in the FAQs before contacting USP. Topic/QuestionContactExpert CommitteeGeneral ChapterKahkashan Zaidi, Ph.D. Senior Scientist1-301-816-8269(GC05) General Chapters 05 重 金 屬本試驗系在規(guī)定的試驗條件下，金屬離子與硫化物離子反應顯色，通過制備的標準鉛溶液目視比較測定，以確證供試品中重金屬雜質含量不超過各論項下規(guī)定的限度（以供試品中鉛的百分比表示，以重量計）。（見分光光度法和光散射項下測定法目視比較法） 注意:對本試驗有響應的典型物質有鉛、汞、鉍、砷、銻、錫、鎘、銀、銅和鉬等 。除各論另有規(guī)定外，按第一法測定重金屬。第一法適用于在規(guī)定試驗條件下，能產生澄清、無色溶液的物質。第二法適用于在第一法規(guī)定試驗條件下不能產生澄清、無色溶液的物質，或者適用于由于性質復雜， 易干擾硫化物離子與金屬離子形成沉淀的物質，或者是不易揮發(fā)的和易揮發(fā)的油類物質。第三法為濕消化法，僅用于第一法、第二法都不適合的情況。特殊試劑硝酸鉛貯備液取硝酸鉛159.8mg， 溶于100ml水中，加1ml硝酸，用水稀釋至1000ml。制備和貯存本溶液的玻璃容器應不含可溶性鉛。標準鉛溶液使用當天，取硝酸鉛貯備液10.0ml， l標準鉛溶液制備的對照溶液，mg的鉛。按每克供試品取100m用水稀釋至100.0ml。每1ml的標準鉛溶液含相當于10 相當于供試品含百萬分之一的鉛。方法 IpH3.5醋酸鹽緩沖液取醋酸銨25.0g溶于25ml水中， 加6N鹽酸液38.0ml， 必要時， 用6N氫氧化銨液或6N鹽酸液調節(jié)pH至3.5， 用水稀釋至100ml， 混勻。g的Pb），m標準溶液準備精密量取標準鉛溶液2ml，（相當于20 置50ml比色管中， 加水稀釋至25ml， 以精密pH試紙作為外指示劑，用1N醋酸液或6N氫氧化銨液調節(jié)pH至3.04.0，用水稀釋至40ml， 混勻。供試品溶液制備取各論項下規(guī)定的供試品溶液25ml， 置50ml比色管中，或用各論項下規(guī)定用量的酸溶解樣品， 再用水稀釋至25ml，供試品以g計，按下式計算：2.0/（1000L）式中L是重金屬限度（%）。以精密pH試紙作為外指示劑，用1N醋酸液或6N氫氧化銨液調節(jié)pH至3.04.0， 用水稀釋至40ml， 搖勻。對照溶液制備取供試品溶液制備項下的溶液25ml， 置50ml比色管中， 加標準鉛溶液2.0ml，以精密pH試紙作為外指示劑，用1N醋酸液或6N氫氧化銨液調節(jié)pH至3.04.0， 用水稀釋至40ml， 搖勻。測定法在上述三試管中，分別加入pH3.5的醋酸鹽緩沖液2ml， 然后再加硫代乙酰胺甘油試液1.2ml，用水稀釋至50ml， 混勻，放置2分鐘， 自上向下觀察：供試品溶液產生的顏色與標準品溶液產生的顏色相比，不得更深。對照溶液產生的顏色比標準溶液深或相當。注意：如果對照溶液的顏色比標準溶液淺，*在白色平面 用方法II代替方法I測定供試品。方法IIpH3.5醋酸鹽緩沖液按方法I配制。標準溶液準備按方法I配制。供試品溶液制備供試品以g計， 按下式計算：2.0/（1000L）式中L是重金屬限度（%）。取供試品適量，稱重， 置適宜的坩堝中，加適量的硫酸使?jié)駶櫍?低溫小心灼燒， 灼燒，直至全部炭化， （在炭化過程中坩堝不可蓋嚴）， 加硝酸2ml和硫酸5滴至炭化物上，