(glye mep' ir ide).
1H-Pyrrole-1-carboxamide, 3-ethyl-2,5-dihydro-4-methyl-N-[2-[4-[[[[(4-methylcyclohexyl)amino]carbonyl]amino]sulfonyl]phenyl]ethyl]-2-oxo-, trans-.
» Glimepiride contains not less than 98.0 percent and not more than 102.0 percent of C24H34N4O5S, calculated on the anhydrous basis.
Packaging and storage Store in well-closed containers, at a temperature not exceeding 25.
USP Reference standards 11
USP Glimepiride Related Compound A RS
USP Glimepiride Related Compound B RS
USP Glimepiride Related Compound C RS
USP Glimepiride Related Compound D RS
Identification, Infrared Absorption 197K.
Water, Method Ic 921 Dissolve about 0.25 g of Glimepiride, accurately weighed, in dimethylformamide previously dried over a molecular sieve (2 mm, pore size 0.4 nm), and dilute with the same solvent to 5.0 mL. Use 1.0 mL of the solution. Perform a blank determination, using 1.0 mL of the solvent. The water content is not more than 0.5%.
Residue on ignition 281: not more than 0.2%.
Heavy metals, Method II 231: 0.001%.
Limit of cis-isomer (glimepiride related compound A)
Mobile phase Transfer 100 mL of isopropyl alcohol into a 1-L volumetric flask, add 1 mL of glacial acetic acid, dilute with hexane to volume, filter, and degas.
System suitability stock solution Dissolve about 1 mg of USP Glimepiride Related Compound A RS in 1 mL of methylene chloride. Add 3 mL of Mobile phase, and mix.
System suitability solution Transfer about 10 mg of USP Glimepiride RS to a 20-mL volumetric flask, and dissolve in 5 mL of methylene chloride. Dilute with Mobile phase to volume, and mix. Transfer 5 mL of this solution to a separate flask, add 50 µL of the System suitability stock solution, and mix.
Test solution Transfer about 10 mg of Glimepiride to a 20-mL volumetric flask, and dissolve in 5 mL of methylene chloride. Dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 228-nm detector and a 3-mm × 15-cm column containing 5-µm packing L20. The flow rate is about 0.5 mL per minute. [noteThe analyses could also be performed with 4.6-mm × 15-cm, 4.6-mm × 25-cm, 4-mm ×12.5-cm, or 4-mm × 25-cm columns containing packing L20. It is recommended that the flow rate be adjusted to about 1.1 mL per minute for a 4.6-mm column and to about 0.8 mL per minute for a 4.0-mm column. ] Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are 1.0 for glimepiride and not more than 0.9 for the glimepiride cis-isomer, and the signal-to-noise ratio of the glimepiride cis-isomer peak is not less than 15.
Procedure Inject about 10 µL of the Test solution into the chromatograph, and measure the peak areas for the glimepiride cis-isomer and glimepiride. Calculate the percentage of glimepiride cis-isomer in the portion of Glimepiride taken by the formula:
100rcis / (rcis + rG)in which rcis and rG are the peak areas for the glimepiride cis-isomer and glimepiride, respectively: not more than 0.8% of the glimepiride cis-isomer is found.
Mobile phase, Diluent, System suitability solution, and Chromatographic system Prepare as directed in the Assay.
Test solution Use the Assay preparation.
Diluted test solution 1 Dilute 5.0 mL of the Test solution with Diluent to 100.0 mL. Dilute 5.0 mL of the solution obtained with Diluent to 50.0 mL. This solution contains about 0.001 mg of glimepiride per mL.
Diluted test solution 2 Dilute 1.0 mL of Diluted test solution 1 with Diluent to 10.0 mL.
Procedure Separately inject equal volumes (about 20 µL) of the Test solution and Diluted test solutions 1 and 2 into the chromatograph, record the chromatograms, and measure the peak response for glimepiride obtained from Diluted test solution 1 and the responses for all other peaks, except the glimepiride peak, obtained from the Test solution. Disregard any peak with an area less than that of the glimepiride peak in the chromatogram obtained from Diluted test solution 2. Continue the elution for 2.5 times the retention time of the glimepiride peak. Calculate the percentage of each related compound (see Table 1) and any unknown impurity in the portion of Glimepiride taken by the formula:
100(CS / CT)(ri / rS)in which CS is the concentration, in mg per mL, of glimepiride in Diluted test solution 1; CT is the concentration, in mg per mL, of glimepiride in the Test solution; ri is the peak response for each individual peak obtained from the Test solution; and rS is the glimepiride peak obtained from Diluted test solution 1.
Mobile phase Dissolve 0.5 g of monobasic sodium phosphate in 500 mL of water. Adjust with phosphoric acid to a pH of 2.1 to 2.7, and add 500 mL of acetonitrile.
Diluent Prepare a mixture of acetonitrile and water (4:1).
Standard preparation Dissolve an accurately weighed quantity of USP Glimepiride RS in Diluent to obtain a solution having a known concentration of about 0.2 mg per mL.
System suitability solution Prepare a solution in Diluent containing 0.1 mg each of USP Glimepiride Related Compound B RS, USP Glimepiride Related Compound C RS, and USP Glimepiride Related Compound D RS per mL. Dilute 1 mL of this solution with the Standard preparation to 50 mL.
Assay preparation Transfer about 20.0 mg of Glimepiride, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix. [noteKeep the Assay preparation at a temperature not exceeding 12, and store it no longer than 15 hours. ]
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 228-nm detector and a 4-mm × 25-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and identify the glimepiride peak and the peaks due to the related compounds listed in Table 1. Record the peak responses as directed for Procedure: the resolution, R, between glimepiride related compound B and glimepiride related compound C is not less than 4.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas of the major peaks. Calculate the percentage of C24H34N4O5S in the portion of Glimepiride taken by the formula:
10,000(C/W)[100/(100 L)](rU / rS)in which C is the concentration, in mg per mL, of USP Glimepiride RS in the Standard preparation; W is the weight, in mg, of Glimepiride taken to prepare the Assay preparation; L is the percentage of water as determined in the test for Water; and rU and rS are the peak responses for the glimepiride obtained from the Assay preparation and the Standard preparation, respectively.
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