Metyrosine Capsules

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

Metyrosine Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of metyrosine (C₁₀H₁₃NO₃). 

2 IDENTIFICATION

A. ULTRAVIOLET ABSORPTION

Sample solution: 0.1 mg/mL solution of the Capsule contents in dilute hydrochloric acid (1 in 100)

Acceptance criteria: The UV absorption spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Metyrosine RS, concomitantly measured.

3 ASSAY

PROCEDURE

Diluent: Dilute hydrochloric acid (1 in 100)

Standard solution: 100 µg/mL of USP Metyrosine RS in Diluent

Sample stock solution: Combine the contents of Capsules (NLT 20), and transfer the nominal equivalent of 100 mg of metyrosine to a 100-mL volumetric flask. Add 50 mL of Diluent, shake by mechanical means for 45 min, dilute with Diluent to volume, and filter.

Sample solution: Nominally 0.1 mg/mL of metyrosine, from Sample stock solution, in Diluent

Spectrometric conditions

Mode: UV

Analytical wavelength: Maximum at about 274 nm

Blank: Dilute hydrochloric acid solution (1 in 100)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of metyrosine (C₁₀H₁₃NO₃) in the portion of Capsules taken: 

                         Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Metyrosine RS in the Standard solution (µg/mL)

C_U = nominal concentration of metyrosine in the Sample solution (µg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1 ▲(RB 22-Sep-2020)

Medium: 0.1 N hydrochloric acid; 750 mL

Apparatus 1: 100 rpm

Time: 60 min

Standard solution: USP Metyrosine RS at a known concentration in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium as needed.

Spectrometric conditions

Mode: UV

Analytical wavelength: Maximum at about 274 nm

Analysis

Samples: Standard solution and Sample solution

Tolerances: NLT 75% (Q) of the labeled amount of metyrosine (C₁₀H₁₃NO₃) is dissolved.

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

4.1.2.1 Tier 1

Medium: 0.1 N hydrochloric acid (degassed); 750 mL

Apparatus 1: 100 rpm. A 20-mesh basket may be used.

Time: 30 min

4.1.2.2 Tier 2

Medium: Transfer 15.09 ± 0.1 g of pepsin (Activity: 371 units/mg) into a suitable container with about 8000 mL of degassed 0.1 N hydrochloric acid. Stir gently to dissolve it and mix well. (Final activity of pepsin in Medium is about 700000 units/L); 750 mL

Apparatus 1: 100 rpm. A 20-mesh basket may be used

Time: 30 min

Standard solution: 0.33 mg/mL of USP Metyrosine RS prepared as follows. Transfer an appropriate amount of USP Metyrosine RS into a suitable volumetric flask. Add methanol to 2%-3% of the flask volume and sonicate to disperse. Add Medium to about 70% of the flask volume, and sonicate to dissolve. Dilute with Medium to volume. [NOTE-Medium in Tier 1 or Tier 2 should be used respectively.]

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 274 nm

Path length: 0.2-cm

Blank: Medium. [NOTE-Medium in Tier 1 or Tier 2 should be used respectively.]

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

Analysis

Perform the test using the conditions in Tier 1. Perform the Tier 2 test only if the Tolerances in Tier 1 can not be met because of the presence of cross-linking in the gelatin. Repeat the test with new Capsules using the conditions in Tier 2.

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of metyrosine (C₁₀H₁₃NO₃) dissolved:

                         Result = (A_U/A_S) × C_S × V  (1/L) × 100

A_U = absorbance from the Sample solution

A_S = absorbance from the Standard solution

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

V = volume of Medium, 750 mL

L = label claim (mg/Capsule)

Tolerances: NLT 80% (Q) of the labeled amount of metyrosine (CH, NO) is dissolved. _{▲(RB 22-Sep-2020)}

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

Add the following:

^▲ LABELING: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used._{▲ (RB 22-Sep-2020)}

USP REFERENCE STANDARDS (11)

USP Metyrosine RS