Levocarnitine Tablets

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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To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click https://www.uspnf.com/rb-levocarnitine-tabs-20240726.

1 DEFINITION

Levocarnitine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of levocarnitine (C₇H₁₅NO₃ ).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. Color Reaction

Analysis: Dissolve 1 Tablet in 5 mL of water, filter, and add 5 mL of 1 N hydrochloric acid. Place 2 mL of the filtrate in a test tube, and add a few drops of ammonium reineckate TS.

Acceptance criteria: A red-violet precipitate is produced.

3 ASSAY

Procedure

Buffer: 0.05 M phosphate buffer, pH 4.5, prepared by dissolving 6.805 g of monobasic potassium phosphate in 1 L of water

Mobile phase: Acetonitrile and Buffer (65:35). Adjust with phosphoric acid to a pH of 4.7, and mix.

System suitability solution: 1.5 mg/mL of USP Levocarnitine RS and 7 μg/mL of USP Levocarnitine Related Compound A RS in water

Standard solution: 3 mg/mL of USP Levocarnitine RS in water

Sample solution: Transfer 10 Tablets, accurately weighed, to a 500-mL volumetric flask, and add water to volume. Shake until the Tablets have disintegrated completely, and pass through a filter of 0.45-μm pore size. Dilute a portion of the filtrate quantitatively with water to a nominal concentration of about 3 mg/mL of levocarnitine.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 205 nm

Column: 3.9-mm × 30-cm; 10-μm packing L8

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.0 between levocarnitine related compound A (crotonoylbetaine) and levocarnitine, System suitability solution

Relative standard deviation: NMT 2.0% for levocarnitine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of levocarnitine (C₇H₁₅NO₃ ) in the portion of Tablets taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak area of levocarnitine from the Sample solution

r_S = peak area of levocarnitine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Test 1 (RB 1-Aug-2024)

Medium: Water; 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Standard solution: Known concentration of USP Levocarnitine RS in Medium

Sample solution: Filtered portion of the solution under test, suitably diluted with Medium if necessary

Analysis

Samples: Standard solution and Sample solution

Proceed as directed in the Assay, making any necessary modifications.

Determine the percentage of the labeled amount of levocarnitine (C₇H₁₅NO₃ ) dissolved:

Result = (r_U/r_S)x(C_S × D × V/L) × 100

r_U = peak area of levocarnitine in the Sample solution

r_S = peak area of levocarnitine in the Standard solution

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

D = dilution factor for the Sample solution

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of levocarnitine (C₇H₁₅NO₃ ) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 1: 100 rpm

Time: 30 min

Solution A: 300 mL of acetonitrile, 700 mL of water, and 1 mL of phosphoric acid

Solution B: Dilute phosphoric acid with water (1:10).

Mobile phase: Sonicate 2.88 g of sodium lauryl sulfate and 2.3 g of monobasic ammonium phosphate in Solution A until dissolved. Adjust with Solution B to a pH of 2.4.

Standard solution: 0.66 mg/mL of USP Levocarnitine RS in Medium

Sample solution: Pass a portion of the solution under test through a 0.45-μm Nylon filter, discarding the first 4 mL of filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 205 nm

Column: 4.6-mm × 7.5-cm; 3.5-μm packing L7

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 100 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 3.0% from 6 replicate injections

Analysis

Samples: Standard solution and Sample solution

Determine the percentage of the labeled amount of levocarnitine (C₇H₁₅NO₃ ) dissolved:

Result = (r_U/r_S)x(C_S × V/L) × 100

r_U = peak area of levocarnitine in the Sample solution

r_S = peak area of levocarnitine in the Standard solution

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

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of levocarnitine (C₇H₁₅NO₃ ) is dissolved.▲ (RB 1-Aug-2024)

Uniformity of Dosage Units 〈905〉: Meet the requirements for Weight Variation

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Levocarnitine RS

USP Levocarnitine Related Compound A RS

2-Propen-1-aminium, 3-carboxy-N,N,N-trimethyl-, chloride.

C₇H₁₄ClNO₂ 179.65