(meth'' il doe' pa).
l-Tyrosine, 3-hydroxy--methyl-, sesquihydrate;
l-3-(3,4-Dihydroxyphenyl)-2-methylalanine sesquihydrate [41372-08-1].
Methyldopa contains NLT 98.0% and NMT 101.0% of C10H13NO4, calculated on the anhydrous basis.
• B. Ultraviolet Absorption 197U
Analytical wavelength: 280 nm
Sample solution: 40 µg/mL in 0.1 N hydrochloric acid
Acceptance criteria: Absorptivities, calculated on the anhydrous basis, do not differ by more than 3.0%.
Sample: 10 mg
Analysis: To the Sample add 0.15 mL of a solution of ninhydrin in sulfuric acid (1 in 250): a dark purple color is produced within 510 min. Add 0.15 mL of water.
Acceptance criteria: The color changes to pale brownish yellow.
Sample solution: 200 mg of Methyldopa in 25 mL of glacial acetic acid, with the aid of heat. Cool to room temperature, and add 0.1 mL of crystal violet TS and 50 mL of acetonitrile.
Analysis: Titrate with 0.1 N perchloric acid VS to a blue endpoint. Perform a blank determination, and make any necessary correction (see Titrimetry 541). Each mL of 0.1 N perchloric acid is equivalent to 21.12 mg of C10H13NO4.
Acceptance criteria: 98.0%101.0% on the anhydrous basis
• Residue on Ignition 281: NMT 0.1%
• Heavy Metals, Method II 231: NMT 10 ppm
• Limit of 3-O-Methylmethyldopa
Standard solution: 100 µg/mL of USP 3-O-Methylmethyldopa RS in methanol
Sample solution: 10 mg/mL of Methyldopa in methanol
Developing solvent system: Butyl alcohol, glacial acetic acid, and water (65:15:25). [NotePrepare this mixture fresh. ]
Adsorbent: Thin-layer chromatographic plate with a suitable grade of cellulose, 250-µm thick, prewashed with the Developing solvent system. Wash the plate by placing it in a tank containing the Developing solvent system, and allowing the solvent to rise to the top of the plate. Dry with the aid of a current of dry air.
Solution A: 3 mg/mL of p-nitroaniline in 10 N hydrochloric acid. [NotePrepare fresh solution, just before use. ]
Solution B: 50 mg/mL of sodium nitrite. [NotePrepare fresh solution, just before use. ]
Spray reagent 1: Solution A and Solution B (9:1). [NotePrepare fresh solution, just before spraying. ]
Spray reagent 2: 250 mg/mL of sodium carbonate
Samples: Standard solution and Sample solution
Apply 20 µL of the Sample solution in two 10-µL increments and 10 µL of the Standard solution so that the spots are NMT 0.5 cm in diameter. Develop using the Developing solvent system until the solvent front has moved about 10 cm from the origin. Remove the plate, and dry with a current of dry air until no odor of acetic acid is perceptible. Place the plate in a vertical position, and evenly spray with Spray reagent 1 until the adsorbent layer is uniformly soaked down to the glass (do not overspray). Place the plate in a horizontal position, and dry as completely as possible with a current of warm dry air (no odor of hydrochloric acid is perceptible). Place the plate in a vertical position, and evenly spray with Spray reagent 2 until the plate is uniformly wet (do not overspray). The major methyldopa spot is black on a pale pink or orange background at an RF value of 0.50, and the 3-O-methylmethyldopa spot is dark on a similar background at an RF value of 0.65.
Acceptance criteria: The area and intensity of any 3-O-methylmethyldopa spot from the Sample solution are NMT those from the Standard solution (0.5%).
• Optical Rotation, Specific Rotation 781S: 25 to 28
Sample solution: 44 mg/mL, in a solvent that is a solution of aluminum chloride in water (2 in 3) that previously has been treated with activated charcoal, filtered, and adjusted with 0.25 N sodium hydroxide to a pH of 1.5
• Acidity: Dissolve 1.0 g in carbon dioxide-free water with the aid of heat, add 1 drop of methyl red TS, and titrate with 0.10 N sodium hydroxide to a yellow endpoint: NMT 0.50 mL is required.
• Water Determination, Method I 921: 10.0%13.0%
• Packaging and Storage: Preserve in well-closed, light-resistant containers.
• USP Reference Standards 11
USP 3-O-Methylmethyldopa RS
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3870Pharmacopeial Forum: Volume No. 37(1)