Methyldopa
C10H13NO4·1½H2O 238.24
C10H13NO4 211.22
l-Tyrosine, 3-hydroxy-
-methyl-, sesquihydrate;
l-3-(3,4-Dihydroxyphenyl)-2-methylalanine sesquihydrate
[41372-08-1].
Anhydrous[555-30-6].
197K
USP35
(meth'' il doe' pa).
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C10H13NO4·1½H2O 238.24
C10H13NO4 211.22
l-Tyrosine, 3-hydroxy-
-methyl-, sesquihydrate;
l-3-(3,4-Dihydroxyphenyl)-2-methylalanine sesquihydrate
[41372-08-1].Anhydrous
[555-30-6].DEFINITION
Methyldopa contains NLT 98.0% and NMT 101.0% of C10H13NO4, calculated on the anhydrous basis.
IDENTIFICATION
Change to read:
• A. Infrared Absorption 197KUSP35
• B. Ultraviolet Absorption 197U
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%.
• C.
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 5–10 min. Add 0.15 mL of water.
Acceptance criteria:
The color changes to pale brownish yellow.
ASSAY
• Procedure
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.
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
IMPURITIES
• Residue on Ignition 281:
NMT 0.1%
281:
NMT 0.1%
• Heavy Metals, Method II 231:
NMT 10 ppm
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
Chromatographic system
Mode:
TLC
Developing solvent system:
Butyl alcohol, glacial acetic acid, and water (65:15:25). [Note—Prepare 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. [Note—Prepare fresh solution, just before use. ]
Solution B:
50 mg/mL of sodium nitrite. [Note—Prepare fresh solution, just before use. ]
Spray reagent 1:
Solution A and Solution B (9:1). [Note—Prepare fresh solution, just before spraying. ]
Spray reagent 2:
250 mg/mL of sodium carbonate
Analysis
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%).
SPECIFIC TESTS
• Optical Rotation, Specific Rotation 781S:
25
to 28
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%
921:
10.0%–13.0%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed, light-resistant containers.
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison 1-301-816-8349 |
(SM22010) Monographs - Small Molecules 2 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3870
Pharmacopeial Forum: Volume No. 37(1)