Add the following:
Pantoprazole Sodium
1H-Benzimidazole, 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-, sodium salt, hydrate (2:3). 5-(Difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]benzimidazole, sodium salt, sesquihydrate [164579-32-2]. » Pantoprazole Sodium contains not less than 98.0 percent and not more than 102.0 percent of C16H14F2N3NaO4S, calculated on the anhydrous basis.
Packaging and storage
Preserve in well-closed, light-resistant containers. Store at room temperature.
Labeling
If a test for Related compounds other than Test 1 is used, then the labeling states the test with which the article complies.
USP Reference standards 11
USP Pantoprazole Sodium RS. USP Pantoprazole Related Compound A RS. USP Pantoprazole Related Compound B RS. USP Pantoprazole Related Compound C RS. USP Pantoprazole Related Compound D and F Mixture RS. USP Pantoprazole Related Compound E RS.
Identification
B:
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
C:
It meets the requirements of the pyroantimonate precipitate test for Sodium 191.
Water, Method I 921:
between 5.0% and 8.0%.
Heavy metals, Method II 231:
not more than 0.002%.
Related compounds
[NoteOn the basis of the synthetic route, perform either Test 1 or Test 2. Test 2 is recommended when impurities C, D, E, and F are potential related compounds.]
test 1
[NoteProtect all solutions from light, and use amber autosampler vials and low-actinic glassware.]
Diluent, Mobile phase, System suitability preparation, and Chromatographic system
Proceed as directed in the Assay.
Standard solution
Transfer about 20 mg of USP Pantoprazole Sodium RS, accurately weighed, to a 50-mL volumetric flask, dissolve in 5 to 10 mL of a mixture of acetonitrile and water (1:1), and dilute with Diluent to volume. Further dilute with Diluent quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.0004 mg per mL.
Test solution
Transfer about 20 mg of Pantoprazole Sodium, accurately weighed, to a 50-mL volumetric flask, dissolve in 5 to 10 mL of a mixture of acetonitrile and water (1:1), dilute with Diluent to volume, and mix.
Chromatographic system
(see Chromatography 621)Prepare as directed in the Assay. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure. Identify the components on the basis of their relative retention times (Table 1): the resolution, R, between the pantoprazole related compound A and pantoprazole peaks is not less than 10.0.
Table 1
Procedure
Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity in the portion of Pantoprazole Sodium taken by the formula:
100(CS / CT)(ri / rS)
in which CS and CT are the concentrations, in mg per mL, of pantoprazole sodium in the Standard solution and the Test solution, respectively; ri is the peak response of each impurity obtained from the Test solution; and rS is the pantoprazole peak response obtained from the Standard solution. The reporting level for impurities is 0.05%.
test 2
Diluent
Prepare a mixture of acetonitrile and 0.001 N sodium hydroxide solution (50:50).
Standard solution
Dissolve an accurately weighed quantity of USP Pantoprazole Sodium RS in Diluent, and dilute quantitatively to obtain a solution having a known concentration of about 0.03 mg per mL.
Test solution
Prepare a solution of Pantoprazole Sodium in Diluent having a known concentration of about 0.46 mg per mL.
System suitability solution
Dissolve suitable amounts of USP Pantoprazole Sodium RS, USP Pantoprazole Related Compound A RS, USP Pantoprazole Related Compound B RS, USP Pantoprazole Related Compound C RS, USP Pantoprazole Related Compound D and F Mixture RS, and USP Pantoprazole Related Compound E RS in Diluent to obtain a solution containing about 0.46 mg of pantoprazole sodium per mL and about 1.3 µg each of related compounds A, B, C, and E per mL, and about 1.3 µg of the D and F mixture per mL.
Solution A
Prepare a solution of dibasic potassium phosphate (1.74 g/L) adjusted with a solution of phosphoric acid (330 g/L) to a pH of 7.00 ± 0.05.
Solution B
Use acetonitrile.
Mobile phase
Use variable mixtures of Solution A and Solution B as directed below for Chromatographic system. Make adjustments as necessary (see System Suitability under Chromatography 621).
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with either a programmable variable wavelength detector or two separate detectors capable of monitoring at 290 nm and at 305 nm, and a 4-mm × 12.5-cm column that contains 5-µm packing L1. The column temperature is maintained at 40. The flow rate is about 1.0 mL per minute. The chromatograph is programmed as follows.
Procedure
Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms at 290 nm and 305 nm, and measure the responses for the major peaks. [NotePantoprazole related compound C is monitored using a wavelength of 305 nm, and all other compounds are monitored at 290 nm.] Calculate the percentage of each impurity in the portion of Pantoprazole Sodium taken by the formula:
100 (1 / F)(CS / CU)(ri / rS)
in which CS is the concentration, in mg per mL, of pantoprazole sodium in the Standard solution; CU is the concentration, in mg per mL of Pantoprazole Sodium in the Test solution; F is the response factor of an individual pantoprazole related compound relative to the response of pantoprazole sodium (Table 2); ri is the peak response of each impurity obtained from the Test solution; and rS is the pantoprazole peak response obtained from the Standard solution. The reporting level for impurities is 0.05%.
Table 2
Assay
[NoteProtect all solutions from light, and use amber autosampler vials and low-actinic glassware.]
Ammonium phosphate buffer
Dissolve 1.32 g of dibasic ammonium phosphate in 1000 mL of water. Adjust with phosphoric acid to a pH of 7.5.
Acetonitrilemethanol mixture
Prepare a mixture of acetonitrile and methanol (7:3).
Solution A
Use a filtered and degassed mixture of Ammonium phosphate buffer and Acetonitrilemethanol mixture (85:15).
Solution B
Use Acetonitrilemethanol mixture.
Diluent
Transfer 25 mL of ammonium hydroxide to a suitable container, and dilute with water to 500 mL.
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 preparation
Dissolve suitable amounts of USP Pantoprazole Sodium RS, USP Pantoprazole Related Compound A RS, and USP Pantoprazole Related Compound B RS in a mixture of acetonitrile and water (1:1) to obtain a solution having about 0.5 mg of each component per mL. Transfer 1 mL of this solution to a 100-mL volumetric flask, and dilute with Diluent to volume.
Standard preparation
Transfer about 20 mg of USP Pantoprazole Sodium RS, accurately weighed, to a 50-mL volumetric flask, dissolve in 5 to 10 mL of a mixture of acetonitrile and water (1:1), and dilute with Diluent to volume. Further dilute with Diluent quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.06 mg per mL.
Assay preparation
Transfer about 20 mg of Pantoprazole Sodium, accurately weighed, to a 50-mL volumetric flask, dissolve in 5 to 10 mL of a mixture of acetonitrile and water (1:1), and dilute with Diluent to volume. Further dilute with Diluent quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.06 mg per mL.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 285-nm detector and 3.9-mm × 15-cm column that contains 4-µm packing L1. The flow rate is about 1 mL per minute. The column temperature is maintained at 30, and the autosampler temperature is maintained at 4. The chromatograph is programmed as follows:
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 C16H14F2N3NaO4S in the portion of Pantoprazole Sodium taken by the formula:
100(CS / CU)(rU / r S)
in which CS and CU are the concentrations, in mg per mL, of pantoprazole sodium in the Standard preparation and the Assay preparation, respectively; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.3
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 3200
Pharmacopeial Forum: Volume No. 33(6) Page 1194
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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