美国药典标准 USP39-NF35Calcium Gluconate Injection

Accessed from 10.6.1.1 by halifax7 on Sat Jan 14 00:54:53 EST 2017USP 39Chromatographic system(See Chromatography 〈621〉, System Suitability.)Mode: Ion chromatographyDetector: ConductanceColumnsGuard: 4-mm × 5-cm; 15-µm packing L12Analytical: 4-mm × 25-cm; 15-µm packing L12Anion suppressor: The micromembrane anion sup-pressor column is connected in series with the guardand analytical columns. The anion suppressor columnis equipped with a micromembrane that separatesMobile phase from Solution A flowing countercurrentto Mobile phase at a rate of about 7mL/min. [NOTE—Condition the system for about 15 min with Mobilephase at a flow rate of 2mL/min.]Flow rate: 2mL/minInjection volume: 50µLSystem suitabilitySample: Standard solutionSuitability requirementsColumn efficiency: NLT 2500 theoretical platesTailing factor: NMT 1.2Relative standard deviation: NMT 2.0%AnalysisSamples: Standard solution and Sample solutionCalculate the percentage of oxalate in the portion ofCalcium Gluconate taken:Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × F × 100= peak response of oxalate from the SamplesolutionrS= peak response of oxalate from the StandardsolutionCS= concentration of sodium oxalate in theStandard solution (µg/mL)CU= concentration of Calcium Gluconate in theSample solution (mg/mL)Mr1= molecular weight of oxalate, 88.03Mr2= molecular weight of sodium oxalate, 134.00F= conversion factor, 0.001mg/µgAcceptance criteria: NMT 0.01%•REDUCING SUBSTANCESSample: 1.0g of Calcium GluconateBlank: 20mL of waterTitrimetric system(See Titrimetry 〈541〉.)Mode: Residual titrationTitrant: 0.1 N iodine VSBack titrant: 0.1 N sodium thiosulfate VSEndpoint detection: VisualAnalysis: Transfer the Sample to a 250-mL conical flask,dissolve in 20mL of hot water, cool, and add 25mL ofalkaline cupric citrate TS. Cover the flask, boil gently for5 min, accurately timed, and cool rapidly to room tem-perature. Add 25mL of 0.6 N acetic acid, 10.0mL ofTitrant, and 10mL of 3N hydrochloric acid. Titrate withthe Back titrant, adding 3mL of starch TS as theendpoint is approached. Perform the ate the percentage of reducing substances (asdextrose) in the Sample taken:Result = {[(VB − VS) × N × F]/W} × 100VBVSNFW= Back titrant volume consumed by the Blank(mL)= Back titrant volume consumed by the Sample(mL)= Back titrant normality (mEq/mL)= equivalency factor, 27mg/mEq= Sample weight (mg)rUOfficial Monographs / Calcium2879Acceptance criteria: NMT 1.0%SPECIFIC TESTS•LOSS

ON DRYING 〈731〉Analysis: Dry at 105° for 16 ance criteriaAnhydrous: NMT 3.0%Monohydrate: NMT 1.0%, where labeled as intendedfor use in preparing injectable dosage forms; NMT2.0%, where labeled as not intended for use in prepar-ing injectable dosage formsADDITIONAL REQUIREMENTS•PACKAGING

AND STORAGE: Preserve in well-closedcontainers.•LABELING: Label it to indicate whether it is anhydrous ormonohydrate. Where the quantity of calcium gluconateis indicated in the labeling of any solution containingCalcium Gluconate, this shall be understood to be interms of anhydrous calcium gluconate (C12H22CaO14).Calcium Gluconate intended for use in preparing inject-able dosage forms is so labeled. Calcium Gluconate notintended for use in preparing injectable dosage forms isso labeled; in addition, it may be labeled also as in-tended for use in preparing oral dosage forms.•USP REFERENCE STANDARDS 〈11〉USP Calcium Gluconate Anhydrous RSUSP Calcium Gluconate Monohydrate RSCalcium Gluconate InjectionDEFINITIONCalcium Gluconate Injection is a sterile solution of CalciumGluconate in Water for Injection. It contains NLT 95.0%and NMT 105.0% of the labeled amount of total calcium is in the form of calcium gluconate, exceptthat a small amount may be replaced with an equalamount of calcium in the form of Calcium Saccharate, orother suitable calcium salts, for the purpose of stabiliza-tion. It may contain sodium hydroxide added for adjust-ment of the ion intended for veterinary use only may be preparedfrom Calcium Gluconate solubilized with Boric Acid, orfrom Gluconolactone, Boric Acid, and Calcium FICATION•A. THIN-LAYER CHROMATOGRAPHYStandard solution: 10mg/mL of USP Potassium Gluco-nate RSSample solution: Dilute a volume of injection, if neces-sary, with water to obtain a concentration of 10mg/mLof calcium tographic system(See Chromatography 〈621〉, System Suitability.)Mode: TLCAdsorbent: 0.25-mm layer of chromatographic silicagelApplication volume: 5µLDeveloping solvent system: Alcohol, ethyl acetate,ammonium hydroxide, and water (50:10:10:30)Spray reagent: Dissolve 2.5g of ammonium molyb-date in 50mL of 2N sulfuric acid in a 100-mL volu-metric flask. Add 1.0g of ceric sulfate, swirl to dis-solve, dilute with 2N sulfuric acid to volume, and isSamples: Standard solution and Sample solutionDevelop the chromatogram until the solvent front hasmoved about three-fourths of the length of the the plate from the chamber, and dry at 110°for 20 min. Allow to cool, and spray with the Sprayreagent. Heat the plate at 110° for about 10 MonographsOfficial from December 1, 2016Copyright (c) 2017 The United States Pharmacopeial Convention. All rights reserved.

Accessed from 10.6.1.1 by halifax7 on Sat Jan 14 00:54:53 EST 20172880Calcium / Official MonographsAcceptance criteria: The principal spot of the Samplesolution corresponds in color, size, and RF value to thatof the Standard solution.•B. IDENTIFICATION TESTS—GENERAL, Calcium 〈191〉Sample solution: Dilute a volume of Injection withwater to obtain a concentration of 20mg/mL of cal-cium ance criteria: Meets the requirementsASSAY•PROCEDURESample: Accurately measured volume of Injection,equivalent to 46.5mg of calciumBlank: 150mL of water containing 2mL of 3N hydro-chloric acidTitrimetric system(See Titrimetry 〈541〉.)Mode: Direct titrationTitrant: 0.05 M edetate disodium VSEndpoint detection: VisualAnalysis: Add 2mL of 3N hydrochloric acid to theSample, and dilute with water to 150mL. While stirring,add 20mL of Titrant from the titration buret. Add15mL of 1N sodium hydroxide and 300mg of hy-droxy naphthol blue, and continue the titration to ablue endpoint. Perform a blank ate the percentage of the labeled amount of totalcalcium in the Sample taken:Result = {[(VS − VB) × M × F]/W} × 100VS= Titrant volume consumed by the Sample (mL)VB= Titrant volume consumed by the Blank (mL)M= Titrant molarity (mmol/mL)F= equivalency factor, 40.08mg/mmolW= weight of calcium in the Sample (mg)Acceptance criteria: 95.0%–105.0%•USP REFERENCE STANDARDS 〈11〉USP Endotoxin RSUSP Potassium Gluconate RSUSP 39Calcium Gluconate TabletsDEFINITIONCalcium Gluconate Tablets contain NLT 95.0% and NMT105.0% of the labeled amount of calcium gluconate(C12H22CaO14).IDENTIFICATION•A. IDENTIFICATION TESTS—GENERAL, Calcium 〈191〉Sample stock solution: A warm, filtered solution inwater, equivalent to 100mg/mL of calcium gluconatefrom powdered TabletsSample solution: Equivalent to 20mg/mL of calciumgluconate from a dilution of the Sample stock solutionAcceptance criteria: Meet the requirements•B. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TESTStandard solution: 10mg/mL of USP Potassium Gluco-nate RSSample solution: Equivalent to 10mg/mL of calciumgluconate from a dilution of the Sample stock solutionobtained from Identification test AChromatographic system(See Chromatography 〈621〉, Thin-Layer Chromato-graphy.)Adsorbent: 0.25-mm layer of chromatographic silicagelApplication volume: 5µLDeveloping solvent system: Alcohol, ethyl acetate,ammonium hydroxide, and water (50:10:10:30)Spray reagent: Dissolve 2.5g of ammonium molyb-date in 50mL of 2N sulfuric acid in a 100-mL volu-metric flask, add 1.0g of ceric sulfate, swirl to dissolve,and dilute with 2N sulfuric acid to isSamples: Standard solution and Sample solutionDevelop until the solvent front has moved about three-fourths of the length of the plate. Remove the plate,and dry at 110° for 20 min. Allow to cool, and spraywith Spray reagent. Heat the plate at 110° for about10 ance criteria: The principal spot of the Samplesolution corresponds in color, size, and RF value to thatof the Standard •PROCEDURESample: A portion of the powder from NLT 20 finelypowdered Tablets, equivalent to 500mg of calciumgluconateBlank: Proceed as directed in the Analysis, without etric system(See Titrimetry 〈541〉.)Mode: Direct titrationTitrant: 0.05 M edetate disodium VSIndicator: Hydroxy naphthol blue, 300mgEndpoint detection: VisualAnalysis: Transfer the Sample to a suitable crucible. Ig-nite, gently at first, until free from carbon. Cool thecrucible. Add 10mL of water, and dissolve the residueby adding sufficient 3N hydrochloric acid, dropwise, toachieve complete solution. Transfer the solution to asuitable container, and add about 150mL of stirring, preferably with a magnetic stirrer, add20mL of Titrant from a 50-mL buret. Add 15mL of 1Nsodium hydroxide, then add the Indicator. Continue thetitration to a blue endpoint. Perform a

MonographsSPECIFIC TESTSChange to read:••BACTERIAL ENDOTOXINS TEST 〈85〉:•(CN 1-May-2016) NMT0.17 USP Endotoxin Units/mg of calcium gluconateChange to read:•Meets the requirements for small-volume injections•PH 〈791〉: 6.0–8.2; 2.5–4.5 where labeled as intended forveterinary use only and as containing boric acidChange to read:•PARTICULATE MATTER

IN INJECTIONS 〈788〉:•(CN 1-May-2016)••INJECTIONS

AND IMPLANTED DRUG PRODUCTS 〈1〉•(CN 1-May-2016): Meets the requirementsADDITIONAL REQUIREMENTS•PACKAGING

AND STORAGE: Preserve in single-dose contain-ers, preferably of Type I glass.•LABELING: Label the Injection to indicate its content, ifany, of added calcium salts, calculated as percentage ofcalcium in the Injection. The label states the total osmo-lar concentration in mOsmol/L. Where the contents areless than 100mL, or where the label states that the Injec-tion is not for direct injection but is to be diluted beforeuse, the label alternatively may state the total osmolarconcentration in mOsmol/mL. The labeling indicates thatthe Injection must be clear at the time of use, and that ifcrystallization has occurred, warming may redissolve theprecipitate. Injection intended for veterinary use only isso labeled. If Injection contains boric acid, it is so al from December 1, 2016Copyright (c) 2017 The United States Pharmacopeial Convention. All rights reserved.