Racemethionine
(rayse'' e me thye' oh neen).
DEFINITION
Racemethionine contains NLT 99.0% and NMT 101.0% of C5H11NO2S, as dl-methionine, calculated on the dried basis.
IDENTIFICATION
• A. Infrared Absorption 197K
Sample:
Dry the substances at 105.
Acceptance criteria:
Meets the requirements
• B.
The principal spot from Sample solution B is similar in size, color, and position to the principal spot from Standard solution A, as obtained in the test for Organic Impurities, Related Substances.
• C. Optical Rotation, Angular Rotation 781A
Sample:
50 mg/mL in 1 M hydrochloric acid
Acceptance criteria:
0.05 to +0.05
• D. Procedure
Analysis:
Dissolve 0.1 g of Racemethionine and 0.1 g of glycine in 4.5 mL of dilute sodium hydroxide solution (85 mg/mL). Add 1 mL of sodium nitroferricyanide solution (25 mg/mL). Heat to 40 for 10 min. Allow to cool, and add 2 mL of a mixture of hydrochloric acid and phosphoric acid (90:10).
Acceptance criteria:
A deep red color develops.
ASSAY
• Procedure
Sample:
140 mg of Racemethionine
Analysis:
Dissolve the Sample in a mixture of 3 mL of formic acid and 50 mL of glacial acetic acid. Titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary corrections (see Titrimetry 541). Each mL of 0.1 N perchloric acid is equivalent to 14.92 mg of C5H11NO2S.
Acceptance criteria:
99.0%101.0% on the dried basis
IMPURITIES
Inorganic Impurities
• Residue on Ignition 281:
NMT 0.1%, determined on 1.0 g
• Chloride and Sulfate, Chloride 221:
[NotePrepare the Sample solution and the Standard solution at the same time. ]
Chloride standard solution (5 ppm Cl):
0.824 mg/mL of NaCl. Just before use, dilute 1 mL of this solution with water to 100 mL.
Standard solution:
To 10 mL of Chloride standard solution add 10 mL of 0.1 N silver nitrate and 25 mL of water, and mix.
Sample solution:
Dissolve 0.25 g in 35 mL of water. Add 5 mL of dilute nitric acid and 10 mL of 0.1 N silver nitrate. Allow to stand protected from light for 5 min.
Analysis:
Examine the Sample solution and Standard solution laterally against a black background.
Acceptance criteria:
Any opalescence in the Sample solution is not more intense than that in the Standard solution (200 ppm).
• Chloride and Sulfate, Sulfate 221:
[NotePrepare the Sample solution and the Control solution at the same time. ]
Barium chloride solution:
250 mg/mL
Sulfate standard solution (10 ppm SO4):
1.81 mg/mL of potassium sulfate in 30% alcohol (v/v). Just before use, dilute 1 mL of this solution with 30% alcohol (v/v) to 100 mL.
Standard solution:
Mix 3 mL of the Barium chloride solution and 4.5 mL of the Sulfate standard solution, and allow to stand for 1 min.
Sample stock solution:
50.0 mg/mL, heated to 60. Cool to 10, and filter.
Sample solution:
To 2.5 mL of the Standard solution add 15 mL of the Sample stock solution and 0.5 mL of 5 N acetic acid.
Control solution:
To 2.5 mL of the Standard solution add 15 mL of the Sulfate standard solution and 0.5 mL of 5 N acetic acid.
Analysis
Samples:
Sample solution and Control solution
Acceptance criteria:
After 5 min, any opalescence in the Sample solution is not more intense than that in the Control solution (200 ppm).
• Heavy Metals
Sodium sulfide solution:
Dissolve 5 g of sodium sulfide in 10 mL of water. Add 30 mL of glycerin.
Standard lead solution:
Prepare as directed for Special Reagents in Heavy Metals 231.
Standard solution:
Transfer 1.0 mL of the Standard lead solution to a 10-mL volumetric flask. Add 1 mL of 50% acetic acid and 2 drops of 25% sodium hydroxide, and dilute with water to volume.
Sample solution:
Dissolve 5 g of Racemethionine by adding 5 mL of 16% hydrochloric acid and 5 mL of water. Adjust with 25% sodium hydroxide to a pH of 3.04.0. Dilute with water to 50 mL. Shake for approximately 15 min, and filter.
Analysis:
Add 1 drop of Sodium sulfide solution to 10 mL of the Sample solution, and add 1 drop of Sodium sulfide solution to 10 mL of the Standard solution. Let stand for 5 min. View downward over a white surface.
Acceptance criteria:
The color of the solution from the Sample solution is not darker than that of the solution from the Standard solution (NMT 10 ppm).
• Limit of Iron
Standard stock solution (125 ppm):
Dissolve 1.727 g of ferric ammonium sulfate [FeNH4(SO4)2·12H2O] in water. Add 50 mL of 10% hydrochloric acid, dilute with water to 1000 mL, and mix. Dilute 1 mL of this solution with water to 40 mL. Pipet 5 mL of this solution into a 200-mL volumetric flask, dilute with water to volume, and mix.
Standard solution:
Transfer 2 mL of the Standard stock solution to a 25-mL volumetric flask. Add 5 mL of 16% hydrochloric acid, 50 mg of ammonium persulfate, and 3 mL of 30% ammonium thiocyanate, and dilute with water to volume.
Sample solution:
Transfer 1 g of Racemethionine to a 25-mL volumetric flask. Add 5 mL of 16% hydrochloric acid, and dissolve. Add 50 mg of ammonium persulfate and 3 mL of 30% ammonium thiocyanate, and dilute with water to volume.
Blank:
Transfer 5 mL of 16% hydrochloric acid to a 25-mL volumetric flask. Add 50 mg of ammonium persulfate and 3 mL of 30% ammonium thiocyanate, and dilute with water to volume.
Spectrometric conditions
Mode:
UV-Vis
Analytical wavelength:
475 nm
Cell:
1 cm
Analysis
Samples:
Standard solution, Sample solution, and Blank
Without delay, concomitantly determine the absorbances of each sample, correcting for the Blank.
Acceptance criteria:
The absorbance of the Sample solution is NMT that of the Standard solution (NMT 10 ppm).
• Limit of Ammonium
Standard solution A:
0.297 mg/mL of USP Ammonium Chloride RS. This solution contains 0.1 mg/mL or 100 ppm of NH4+.
Standard solution B:
0.297 µg/mL of USP Ammonium Chloride RS. This solution contains 0.1 µg/mL or 0.1 ppm of NH4+.
Standard solution C:
2.97 µg/mL of USP Ammonium Chloride RS. This solution contains 1.0 µg/mL or 1 ppm of NH4+.
Standard solution D:
29.7 µg/mL of USP Ammonium Chloride RS. This solution contains 10 µg/mL or 10 ppm of NH4+.
Sample solution:
10 mg/mL of Racemethionine
Electrode system:
Use an ammonia-specific,1 ion-indicating electrode connected to a pH meter capable of measuring potentials (see pH 791).
Analysis
Samples:
Standard solution A, Standard solution B, Standard solution C, Standard solution D, and Sample solution
Add 100 mL of water to a 150-mL beaker, place the electrode in the beaker, stir, and measure the potential. Add 1 mL of 10 N sodium hydroxide. Stir, and measure the potential after stabilization. [NoteIt may take about 5 min. ] The potential difference must be less than 20 mV.
Add 100.0 mL each of Standard solutions A, B, C, and D to four different 150-mL beakers. To each beaker, add 1 mL of 10 N sodium hydroxide. Place the ammonia electrode in the beaker, stir, and concomitantly measure the potential after stabilization. [NoteIt may take about 5 min. ] Draw a calibration curve of the potential, in mV, versus, the quantity of ammonium (NH4+), in mg.
Add 100.0 mL of the Sample solution to a 150-mL beaker. Add 1 mL of 10 N sodium hydroxide. Adjust the pH, if necessary, with 10 N sodium hydroxide to a pH of NLT 11. Place the ammonia electrode in the beaker, stir, and measure the potential after stabilization. [NoteIt may take about 5 min. ] Obtain the quantity of NH4+, in mg, in the 100 mL of the Sample solution based on the calibration curve.
Calculate the percentage of ammonium (NH4+), in the portion of Racemethionine taken:
Result = (C/W) × F
Acceptance criteria:
NMT 200 ppm
Organic Impurities
• Procedure: Related Substances
Standard solution A:
0.40 mg/mL of USP Racemethionine RS
Standard solution B:
40 µg/mL of USP Racemethionine RS
Sample solution A:
20 mg/mL of Racemethionine
Sample solution B:
0.40 mg/mL of Racemethionine
Chromatographic system
Mode:
TLC
Adsorbent:
0.25-mm layer of chromatographic silica gel mixture
Application volume:
5 µL
Developing solvent system:
Butyl alcohol, glacial acetic acid, and water (3:1:1)
Spray reagent:
2 mg/mL of ninhydrin in a mixture of butyl alcohol and 2 N acetic acid (95:5)
Analysis
Samples:
Standard solution A, Standard solution B, Sample solution A, and Sample solution B
Develop over a path of 10 cm using the Developing solvent system. After air-drying the plate, spray with Spray reagent, and heat between 100 and 105 for 15 min. Examine the plate under white light.
Acceptance criteria:
Any spot obtained from Sample solution A, apart from the principal spot, is not more intense than the spot obtained from Standard solution B (NMT 0.2%).
SPECIFIC TESTS
• pH 791:
5.46.1, in a 20 mg/mL solution
• Loss on Drying 731:
Dry a sample at 105 for 3 h: it loses NMT 0.5% of its weight, determined on 1.000 g.
• Transmittance
Sample solution:
10% of Racemethionine in 2 N hydrochloric acid, prepared by sonication
Analysis:
Determine the transmittance in a 1-cm cell at 430 nm with a suitable spectrophotometer.
Acceptance criteria:
Transmittance of NLT 0.98, corresponding to an absorbance of NMT about 0.009
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, protected from light.
1
Orion 95-12 is suitable.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 1939
Pharmacopeial Forum: Volume No. 36(5) Page 1236
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