(oh mep' ra zole mag nee' zee um).
(RS)-5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole, magnesium salt (2:1).
5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]benzimidazole, (RS), magnesium salt (2:1) [95382-33-5].
» Omeprazole Magnesium contains not less than 97.5 percent and not more than 102.0 percent of C34H36MgN6O6S2, calculated on the anhydrous basis.
Packaging and storage Preserve in tight containers, protected from light. Store at room temperature.
USP Reference standards 11
USP Omeprazole Related Compound A RS
Omeprazole sulfone, 5-methoxy-2-[[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfonyl]-1H-benzimidazole.
B: The Test solution, prepared and tested as directed in the test for Content of magnesium, exhibits a significant absorption at the magnesium emission line at 285.2 nm.
Color of solution Prepare a solution of Omeprazole Magnesium in methanol having a concentration of 20 mg per mL, and filter. Determine the absorbance of this solution at 440 nm, in 1-cm cells, using methanol as the blank: the absorbance is no greater than 0.1.
Water, Method I 921: between 7% and 10%.
Specific rotation 781S: between +0.5 and 0.5, measured at 20.
Test solution: 10 mg per mL, in methanol.
Phosphate buffer pH 7.6 Prepare as directed in the Assay.
Mobile phase Prepare a filtered and degassed mixture of Phosphate buffer pH 7.6 and acetonitrile (72.5:27.5). Make adjustments if necessary (see System Suitability under Chromatography 621). [noteTo improve the resolution, the composition may be changed to 75:25, if necessary. ]
Test solution Dissolve about 4 mg of Omeprazole Magnesium in 25 mL of the Mobile phase. [notePrepare this solution fresh. ]
System suitability solution Dissolve about 1 mg of USP Omeprazole RS and 1 mg of USP Omeprazole Related Compound A RS in about 25 mL of Mobile phase. [noteOmeprazole related compound A is omeprazole sulfone. ]
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 280-nm detector and a 4.0-mm × 12.5-cm or 4.6-mm × 15-cm column that contains 5-µm packing L7. (Alternatively, a 3.9-mm × 15-cm column that contains 4-µm packing L1 may be used.) The flow rate is about 0.8 to 1.0 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times for omeprazole related compound A and omeprazole are about 0.8 and 1.0, respectively; and the resolution, R, between omeprazole related compound A and omeprazole is not less than 3.
Procedure Inject a volume (about 50 µL) of the Test solution into the chromatograph, record the chromatogram for at least 4.5 times the retention time of omeprazole, and measure the peak responses. Identify the impurities based on the relative retention times listed in Table 1.
100(ri / rs)in which ri is the peak response of any individual impurity; and rs is the sum of the responses of all the peaks: in addition to not exceeding the limits in Table 1, not more than 0.1% of any other individual impurity is found; and not more than 0.5% of total impurities is found.
Content of magnesium
Lanthanum solution Transfer 58.7 g of lanthanum oxide to a 1000-mL volumetric flask, wet the substance with some water, and dissolve by cautious addition of 250 mL of hydrochloric acid in 20- to 30-mL portions, cooling between additions. Add water while stirring, cool to room temperature, and dilute with water to volume. [noteStore the solution in a plastic bottle. ]
Magnesium standard stock solution Quantitatively dilute a suitable amount of a commercially prepared atomic absorption standard solution for magnesium with water to obtain a solution containing 1000 µg of magnesium per mL. [noteStore the solution in a plastic bottle. ]
Magnesium intermediate standard solution Transfer 10.0 mL of Magnesium standard stock solution to a 500-mL volumetric flask, add 50 mL of 1 N hydrochloric acid, and dilute with water to volume. Transfer 20.0 mL of this solution to a 200-mL volumetric flask, and dilute with water to volume. This solution contains 2 µg of magnesium per mL.
Standard solutions Transfer 5.0, 10.0, 15.0, 20.0, and 25.0 mL of Magnesium intermediate standard solution to separate 100-mL volumetric flasks. To each flask, add 4.0 mL of Lanthanum solution, and dilute with water to volume. These Standard solutions contain 0.1, 0.2, 0.3, 0.4, and 0.5 µg of magnesium per mL, respectively. [noteConcentrations of the Standard solutions and the Test solution may be modified to fit the linear or working range of the instrument. When using instruments with a linear calibration graph, the number of the Standard solutions can be reduced. ]
Blank solution Transfer 4.0 mL of Lanthanum solution to a 100-mL volumetric flask, and dilute with water to volume.
Test solution Transfer about 250 mg of Omeprazole Magnesium, accurately weighed, to a 100-mL volumetric flask, add 20 mL of 1 N hydrochloric acid, swirl until dissolved, and dilute with water to volume. Allow to stand for 30 minutes. Transfer 10.0 mL of this solution to a 200-mL volumetric flask, and dilute with water to volume. Transfer 10.0 mL of the solution so obtained to another 100-mL volumetric flask, add 4.0 mL of Lanthanum solution, and dilute with water to volume.
Procedure Concomitantly determine the absorbances of the Standard solutions, the Blank solution, and the Test solution at the magnesium emission line at 285.2 nm with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering 851) using an airacetylene flame. Determine the concentration, C, in µg per mL, of magnesium in the Test solution using the calibration graph. Calculate the content of magnesium, in percentage, in the portion of Omeprazole Magnesium taken by the formula:
100(0.001CD / W)[100 / (100 L)]in which the multiplier 0.001 is for conversion of µg per mL to mg per mL; C is as defined above; D is the dilution factor for the Test solution; W is the quantity of Omeprazole Magnesium, in mg, taken to prepare the Test solution; and L is the content of water, in percentage, as determined in the test for Water. The magnesium content, calculated on the anhydrous basis, is between 3.30% and 3.55%.
Phosphate buffer pH 7.6 Dissolve 0.725 g of monobasic sodium phosphate and 4.472 g of anhydrous dibasic sodium phosphate in 300 mL of water, dilute with water to 1000 mL, and mix. Dilute 250 mL of this solution with water to 1000 mL. If necessary, adjust with phosphoric acid to a pH of 7.6.
Mobile phase Prepare a mixture of Phosphate buffer pH 7.6 and acetonitrile (650:350).
Phosphate buffer pH 11 Mix 11 mL of 0.25 M tribasic sodium phosphate with 22 mL of 0.5 M dibasic sodium phosphate, and dilute with water to 100 mL.
Standard preparation Transfer about 10 mg of USP Omeprazole RS, accurately weighed, to a 200-mL volumetric flask, and dissolve in about 10 mL of methanol. Add 10 mL of Phosphate buffer pH 11, and dilute with water to volume. This solution contains about 0.05 mg of omeprazole per mL.
Assay preparation Transfer about 10 mg of Omeprazole Magnesium, accurately weighed, to a 200-mL volumetric flask, dissolve in about 10 mL of methanol, add 10 mL of Phosphate buffer pH 11, and dilute with water to volume. This solution contains about 0.05 mg of omeprazole magnesium per mL.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 280-nm detector and a 4.0-mm × 12.5-cm or 4.6-mm × 15-cm column that contains 5-µm packing L7. (Alternatively, a 3.9-mm × 15-cm column that contains 4-µm packing L1 may be used.) The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 2000 theoretical plates; and 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 responses for the major peaks. Calculate the percentage of C34H36MgN6O6S2 in the portion of Omeprazole Magnesium taken by the formula:
100[(713.12 / (2 × 345.42)](CS / CU)(rU / rS)in which 713.12 and 345.42 are the molecular weights of omeprazole magnesium and omeprazole, respectively; CS is the concentration, in mg per mL, of omeprazole in the Standard preparation; CU is the concentration, in mg per mL, of omeprazole magnesium in the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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