Morphine Sulfate Compounded Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Morphine Sulfate Compounded Injection contains NLT 90.0% and NMT 110.0% of the labeled amount of morphine sulfate pentahydrate [(C₁₇H₁₉NO₃)₂ · H₂SO₄ · 5H₂O].

Prepare Morphine Sulfate Compounded Injection, 10 or 50 mg/mL, as follows (see Pharmaceutical Compounding-Sterile Preparations (797)).

10-mg/mL Morphine Sulfate Compounded Injection

^a Morphine Sulfate, USP, is morphine sulfate pentahydrate; therefore no additional calculation is needed to account for the waters of hydration.

50-mg/mL Morphine Sulfate Compounded Injection

^a Morphine Sulfate, USP, is morphine sulfate pentahydrate; therefore no additional calculation is needed to account for the waters of hydration.

Dissolve the Morphine sulfate pentahydrate and Sodium Chloride in Sterile Water for Injection in a suitable calibrated container. Add sufficient Sterile Water for Injection to bring to final volume and mix well. Pass through a sterile filter of 0.22-µm pore size into sterile container(s).

2 ASSAY

PROCEDURE

Solution A: Dissolve 5.44 g of dibasic potassium phosphate in 800 mL of water and add 200 mL of methanol.

Mobile phase: See Table 1.

Table 1

Standard solution: 1 mg/mL of morphine sulfate pentahydrate prepared from USP Morphine Sulfate RS in water

Sample solution: Transfer 0.4 mL of the Injection into a 100-mL volumetric flask, and dilute with water to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 15 µL

System suitability

Sample: Standard solution

[NOTE-The retention time for morphine sulfate is about 10.5 min.]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of morphine sulfate pentahydrate [(C₁₇H₁₉NO₃)₂ · H₂SO₄ · 5H₂O] in the portion of Injection 

taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution 

C_S = concentration of USP Morphine Sulfate RS in the Standard solution (mg/mL)

C_U = nominal concentration of morphine sulfate pentahydrate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

3 SPECIFIC TESTS

PH (791): 2.5-6.5

Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements

BACTERIAL ENDOTOXINS TEST (85): It contains NMT 17.0 USP Endotoxin Units/mg of morphine sulfate. If labeled for intrathecal use, it contains NMT 14.29 USP Endotoxin Units/mg of morphine sulfate.

PARTICULATE MATTER IN INJECTIONS (788): It meets the requirements.

4 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Package in sterile syringes for single-use in one patient only, protected from light. Store at controlled room temperature.

Change to read:

BEYOND-USE DATE: ^▲In the absence of performing and completing a sterility and endotoxin test, the storage conditions in Pharmaceutical Compounding - Sterile Preparations (797), 14.3 Establishing a BUD for a CSP apply- _{▲(CN 1-Nov-2023)} After successful completion of sterility and endotoxin testing, NMT 90 days after the date on which it was compounded when stored at controlled room temperature.

LABELING: Label it to indicate that it is for use in a single patient only. Label it to indicate that it is preservative-free. Label it to state the Beyond-Use Date.

USP REFERENCE STANDARDS (11).

USP Morphine Sulfate RS