Morphine Sulfate Compounded Oral Solution

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 Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of morphine sulfate pentahydrate (C₁₇H₁₉NO₃)₂ · H₂SO₄ · 5H₂O.

Prepare Morphine Sulfate Compounded Oral Solution, 0.4 mg/mL, as follows¹ (see Pharmaceutical Compounding-Nonsterile Preparations (795)).

^a Morphine Sulfate Oral Solution 2 mg/mL, Roxane Laboratories, Columbus, OH.

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

Measure Morphine Sulfate Oral Solution into a calibrated container. Add a sufficient amount of Purified Water to final volume. Shake to mix well.

2 ASSAY

PROCEDURE

Solution A: A solution of 5.44 g/L of potassium phosphate dibasic in water, adjusted with phosphoric acid to a pH of 5.8. Pass through a polyvinyl difluoride filter of 0.22-µm pore size.

Mobile phase: See Table 1.

Table 1

Standard solution: 0.1 mg/mL of USP Morphine Sulfate RS in water. Sonicate for 1 min and shake for 2 min.

Sample solution: Vortex the bottle for 1 min, then allow 1 min for bubbles to dissipate. Transfer about 8 mL of solution into a plastic cup. Transfer 5.0 mL with a class A glass pipette into a 20-mL volumetric flask. Rinse the pipette 2 times using water and transfer the contents into the volumetric flask. Bring to volume with water. Vortex at least for 2 min.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 284 nm

Column: 4.6-mm x 15-cm; 3-µm packing L1

Temperatures

Autosampler: 10°

Column: 35°

Flow rate: 1 mL/min

Injection volume: 40 µL

System suitability

Sample: Standard solution

[NOTE-The retention time for morphine sulfate is about 13.5 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 Oral Solution taken:

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

r_U = peak response of morphine sulfate from the Sample solution

r_S = peak response of morphine sulfate 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 in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110%

3 SPECIFIC TESTS

PH (791): 2.9-3.9

Appearance: Clear, blue solution with no particulates

4 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Package in tight, light-resistant, plastic containers. Store in a refrigerator or at controlled room temperature.

BEYOND-USE DATE: NMT 90 days after the date on which it was compounded when stored at controlled room temperature or in a refrigerator.

LABELING: Label to indicate the Beyond-Use Date.

USP REFERENCE STANDARDS (11)

USP Morphine Sulfate RS _{▲(USP 1-Aug-2023)}

¹ This formulation meets the requirements in Antimicrobial Effectiveness Testing (51)