Meloxicam
4-Hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide [71125-38-7]. » Meloxicam contains not less than 99.0 percent and not more than 100.5 percent of C14H13N3O4S2, calculated on the dried basis.
Packaging and storage
Preserve in well-closed containers. Store at room temperature.
Labeling
The labeling states with which Related compounds test the article complies if a test other than Test 1 is used.
USP Reference standards 11
USP Meloxicam RS . USP Meloxicam Related Compound A RS . USP Meloxicam Related Compound B RS . USP Meloxicam Related Compound C RS . USP Meloxicam Related Compound D RS .
Identification
B:
Ultraviolet Absorption 197U.
Spectral range:
240 to 450 nm.
Solution:
10 µg per mL.
Medium:
methanol.
Loss on drying 731
Dry it at 105 for 4 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281:
not more than 0.1%.
Heavy metals, Method II 231:
not more than 0.001%.
Related compounds
[notePerform either Test 1 or Test 2 depending on the manufacturing process used.]
test 1
Solution A:
a 0.1% (w/v) solution of monobasic potassium phosphate adjusted with 1 N sodium hydroxide to a pH of 6.0.
Solution B:
methanol.
Mobile phase
Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution
Transfer about 4 mg of USP Meloxicam RS and about 4 mg each of USP Meloxicam Related Compound A RS and USP Meloxicam Related Compound B RS into a 50-mL volumetric flask, dissolve in 5 mL of methanol and 0.3 mL of 1 N sodium hydroxide, dilute with methanol to volume, and mix.
Standard solution
Transfer about 12 mg of USP Meloxicam RS, accurately weighed, to a 20-mL volumetric flask, dissolve in 5 mL of methanol and 0.3 mL of 1 N sodium hydroxide, dilute with methanol to volume, and mix. Transfer 2 mL of this solution to a 100-mL volumetric flask, dilute with methanol to volume, and mix.
Test solution
Transfer about 80 mg of Meloxicam, accurately weighed, to a 20-mL volumetric flask, dissolve in 5 mL of methanol and 0.3 mL of 1 N sodium hydroxide, dilute with methanol to volume, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a variable wavelength or multi-wavelength UV detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The column temperature is maintained at 45. The flow rate is about 1 mL per minute, and the detection wavelengths are 260 nm and 350 nm. The chromatograph is programmed as follows.
Procedure
Separately inject equal volumes (about 5 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms at detection wavelengths of 260 nm and 350 nm, and measure the peak responses. Calculate the percentage of each impurity in the portion of Meloxicam taken by the formula:
100(CS / CT)(1 / F)(rU / rS)
in which CS is the concentration, in mg per mL, of USP Meloxicam RS in the Standard solution; CT is the concentration, in mg per mL, of Meloxicam in the Test solution; F is the relative response factor (see Table 1); rU is the peak response of each impurity obtained from the Test solution; and rS is the peak response of meloxicam at 350 nm obtained from the Standard solution. [noteFor the specified impurities, calculate the percentage content of each impurity, using the Test solution peak responses recorded at the detection wavelength given in Table 1. For an unknown impurity, calculate the percentage content, using peak responses recorded at the wavelength that gives the greater response.]
Table 1
test 2
If an article complies with this test, the labeling indicates that it meets the requirements of Related compounds Test 2.
Solution A and Solution B
Prepare as directed in Test 1.
Mobile phase
Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent A:
a mixture of Diluent B and 0.4 N sodium hydroxide (50:3).
Diluent B:
a mixture of water and methanol (60:40).
Standard stock solution 1
Prepare a solution having a known concentration of about 50 µg per mL of USP Meloxicam RS in Diluent A. Transfer 2 mL of the solution to a 10-mL volumetric flask, dilute with Diluent B to volume, and mix.
Standard stock solution 2
Transfer about 5 mg each of USP Meloxicam Related Compound B RS, USP Meloxicam Related Compound C RS, and USP Meloxicam Related Compound D RS into a 100-mL volumetric flask, add 6 mL of 0.4 N sodium hydroxide, and sonicate for about 2 minutes. Add 40 mL of methanol to the resulting solution, sonicate for about 2 minutes, dilute with water to volume, and mix.
Standard solution
Transfer 1 mL each of Standard stock solution 1 and Standard stock solution 2 into a 10-mL volumetric flask, dilute with Diluent B to volume, and mix.
System suitability stock solution
Prepare a solution containing about 2 mg per mL of USP Meloxicam RS in Diluent A.
System suitability solution
Transfer 5 mL of System suitability stock solution and 1 mL of Standard stock solution 2 into a 10-mL volumetric flask, dilute with Diluent B to volume, and mix.
Test solution
Transfer about 20 mg of Meloxicam, accurately weighed, to a 20-mL volumetric flask, dissolve in 10 mL of Diluent A, dilute with Diluent B to volume, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a variable wavelength or multi-wavelength UV detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The column temperature is maintained at 45. The flow rate is about 1 mL per minute and the detection wavelengths are 260 nm and 350 nm. The chromatograph is programmed as follows.
Procedure
Separately inject equal volumes (about 20 µL) of the Standard solution and Test solution into the chromatograph, record the chromatograms at detection wavelengths of 260 nm and 350 nm, and measure the peak responses. Calculate the percentage of each impurity in the portion of Meloxicam taken by the formula:
100(CS / CT)(rU / rS)
in which CS is the concentration, in mg per mL, of the corresponding USP Related Compound RS in the Standard solution [noteUse the concentration of the USP Meloxicam RS for unknown impurities.]; CT is the concentration, in mg per mL, of Meloxicam in the Test solution; rU is the peak response of each impurity obtained from the Test solution; and rS is the peak response of the corresponding related compound obtained from the Standard solution. [noteUse the peak response of the USP Meloxicam RS for unknown impurities; for the specified impurities, calculate the percentage content of each impurity using the Test solution peak responses recorded at the detection wavelength given in Table 2. For an unknown impurity, calculate the percentage content using peak responses recorded at the wavelength that gives the greater response.]
Table 2
Assay
Buffer solution:
a mixture of a 0.1% (w/v) solution of ammonium acetate adjusted with 10% ammonia solution to a pH of 9.1.
Mobile phase
Prepare a filtered and degassed mixture of Buffer solution and methanol (58:42). Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution
Transfer about 4 mg of USP Meloxicam RS and about 4 mg of USP Meloxicam Related Compound A RS into a 50-mL volumetric flask, dissolve in 25 mL of methanol and 0.1 mL of 1 N sodium hydroxide, dilute with water to volume, and mix.
Standard preparation
Transfer about 20 mg of USP Meloxicam RS, accurately weighed, into a 100-mL volumetric flask, dissolve in 50 mL of methanol and 0.2 mL of 1 N sodium hydroxide, dilute with water to volume, and mix.
Assay preparation
Transfer about 20 mg of Meloxicam, accurately weighed, into a 100-mL volumetric flask, dissolve in 50 mL of methanol and 0.2 mL of 1 N sodium hydroxide, dilute with water to volume, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 360-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The column temperature is maintained at 45. The flow rate is about 1.0 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for related compound A and 1.0 for meloxicam; the resolution, R, between the two peaks is not less 3.0; the tailing factor for the meloxicam peak is not more than 2.0; and the relative standard deviation for replicate injections, calculated for the meloxicam peak, is not more than 2.0%.
Procedure
Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the meloxicam peak. Calculate the quantity, in mg, of C14H13N3O4S2 in the portion of Meloxicam taken by the formula:
100C(rU / rS)
in which C is the concentration, in mg per mL, of USP Meloxicam RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 2870
Pharmacopeial Forum: Volume No. 31(1) Page 57
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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