Morphine Sulfate Injection
»Morphine Sulfate Injection is a sterile solution of Morphine Sulfate in Water for Injection.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of morphine sulfate pentahydrate [(C17H19NO3)2·H2SO4·5H2O].Injection intended for intramuscular or intravenous administration may contain sodium chloride as a tonicity-adjusting agent,and suitable antioxidants and antimicrobial agents.Injection intended for intrathecal or epidural use may contain sodium chloride as a tonicity-adjusting agent,but contains no other added substances.
Packaging and storage— Preserve in single-dose or in multiple-dose containers,preferably of Type Iglass,protected from light.Preserve Injection labeled “Preservative-free”in single-dose containers.
Labeling— It meets the requirements for Labelingunder Injections á1ñ.Label it also to state that the Injection is not to be used if its color is darker than pale yellow,if it is discolored in any other way,or if it contains a precipitate.Injection containing no antioxidant or antimicrobial agents prominently bears on its label the words “Preservative-free,”and includes,in its labeling,its routes of administration and the statement that it is not to be heat-sterilized.Injection containing antioxidant or antimicrobial agents includes in its labeling its routes of administration and the statement that it is not for intrathecal or epidural use.
Identification—
A: Dilute with methanol,if necessary,a volume of Injection to obtain a solution containing 500µg per mL.Apply 20µLof this solution and 20µLof a solution of USP Morphine Sulfate RSin a mixture of methanol and water (1:1)containing 500µg per mLto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 250-µm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of acetone,methanol,and ammonium hydroxide (50:50:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Locate the spots on the plate by examination under short-wavelength UVlight:the RFvalue of the principal spot obtained from the Injection corresponds to that obtained from the Standard solution.
B: It responds to the barium chloride test for Sulfate á191ñ.
Bacterial endotoxins á85ñ— It contains not more than 17.0USP Endotoxin Units per mg of morphine sulfate;if labeled for intrathecal use,it contains not more than 14.29USP Endotoxin Units per mg of morphine sulfate.
pHá791ñ: between 2.5and 6.5.
Particulate matter á788ñ— meets the requirements under small-volume Injections.
Other requirements— It meets the requirements under Injections á1ñ.
Assay—
Mobile phase ,Standard preparation,System suitability preparation,and Chromatographic system—Prepare as directed in the Assayunder Morphine Sulfate.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 24mg of morphine sulfate,to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Procedure— Proceed as directed for Procedurein the Assayunder Morphine Sulfate.Calculate the quantity,in mg,of morphine sulfate pentahydrate [(C17H19NO3)2·H2SO4·5H2O]in each mLof the Injection taken by the formula:
(758.85/668.77)(100C/V)(rU/rS),
in which 758.85and 668.77are the molecular weights of morphine sulfate pentahydrate and anhydrous morphine sulfate,respectively,Vis the volume,in mL,of Injection taken,and the other terms are as defined therein.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28–NF23Page 1315
Phone Number:1-301-816-8139