Leucovorin Calcium Compounded Oral Suspension

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

Leucovorin Calcium Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of leucovorin (C₂₀H₂₃N₇O₇ ).

Prepare Leucovorin Calcium Compounded Oral Suspension containing 5 mg/mL of leucovorin as follows (see Pharmaceutical Compounding— Nonsterile Preparations 〈795〉).

^a Leucovorin calcium 25-mg tablets, Teva Pharmaceuticals, Sellersville, PA.

Place the Leucovorin Calcium tablets into a suitable container. Wet the tablets with a small amount of Syrup and triturate to make a smooth paste. Add the Syrup to make the contents pourable. Transfer contents stepwise and quantitatively to a calibrated container using the Syrup.

Adjust with Sodium Hydroxide (1 N) to a pH of 7.1–7.6. Add sufficient Syrup to bring to final volume. Shake to mix well. [Note—pH may decrease to 6.1 after bringing to final volume with Syrup without affecting the stability of the preparation.]

2 ASSAY

Procedure

Solution A: Methanol and 5 mM tetrabutylammonium phosphate (20:80). Adjust with tetrabutylammonium hydroxide to a pH of 6.6. [Note—

Tetrabutylammonium phosphate appearing wet should not be used as it may coelute with leucovorin.]

Mobile phase: See Table 1.

Table 1

Diluent: Methanol and water (20:80)

Standard solution: 0.05 mg/mL of leucovorin prepared from USP Leucovorin Calcium RS and Diluent. Vortex and sonicate until dissolved.

Sample solution: Transfer 1.0 mL of Oral Suspension to a 100-mL volumetric flask, and rinse the pipette with about 2 mL of Diluent. Dilute with Diluent to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 290 nm

Column: 4.6-mm × 15-cm; 2.7-μm packing L7

Column temperature: 55°

Flow rate: 0.75 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

[Note—The retention time for leucovorin is about 20.3 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 leucovorin (C₂₀H₂₃N₇O₇ ) in the portion of Oral Suspension taken:

Result = (r_U/r_S)x(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 leucovorin from USP Leucovorin Calcium RS in the Standard solution (mg/mL)

C_U = nominal concentration of leucovorin in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 6.1–7.1

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 in a refrigerator; NMT 30 days after the date on which it was compounded when stored at controlled room temperature

Labeling: Label it to be well shaken before use, and to state the Beyond-Use Date.

USP Reference Standards 〈11〉

USP Leucovorin Calcium RS