Cefaclor Capsules
» Cefaclor Capsules contain the equivalent of not less than 90.0 percent and not more than 120.0 percent of the labeled amount of C15H14ClN3O4S.
Packaging and storage— Preserve in tight containers.
USP Reference standards 11
USP Cefaclor RS Click to View Structure
USP Cefaclor Delta-3 Isomer RS
Identification— 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.
Dissolution 711
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure— Determine the amount of cefaclor (C15H14ClN3O4S) dissolved from UV absorbances at the wavelength of maximum absorbances at about 264 nm of filtered portions of the solution under test, suitably diluted with water, in comparison with a Standard solution having a known concentration of USP Cefaclor RS in the same medium.
Tolerances— Not less than 80% (Q) of the labeled amount of cefaclor (C15H14ClN3O4S) is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Water, Method I 921: not more than 8.0%.
Related compounds—
Diluent— Dissolve 2.4 g of monobasic sodium phosphate in 1000 mL of water, and adjust with phosphoric acid to a pH of 2.5.
Blank solution— Use the Diluent.
Solution A— Dissolve 6.9 g of monobasic sodium phosphate in 1000 mL of water, and adjust with phosphoric acid to a pH of 4.0.
Solution B— Prepare a mixture of Solution A and acetonitrile (55:45), degassing for no longer than 2 minutes.
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). [note—Reducing the acetonitrile content increases the retention time of cefaclor and increases the resolution between the delta-3 isomer and cefaclor. ]
Standard solution— Dissolve an accurately weighed quantity of USP Cefaclor RS in Diluent to obtain a solution having a known concentration of about 0.05 mg per mL of cefaclor. Sonicate briefly, if necessary, to dissolve, and avoid heating. [note—Use this solution on the day it is prepared. ]
System suitability solution— Dissolve a quantity of USP Cefaclor, Delta-3 Isomer RS in the Standard solution to obtain a solution having a known concentration of about 0.05 mg per mL of the delta-3 isomer.
Test solution— Remove as completely as possible the contents of not fewer than 20 Capsules, and mix. Transfer an accurately weighed portion of the combined contents, equivalent to about 50 mg of cefaclor, to a 10-mL volumetric flask. Dissolve in Diluent, using brief sonication, if necessary, to achieve dissolution. Avoid heating. Dilute with Diluent to volume, mix, and filter. This solution has a nominal concentration of 5 mg per mL based on the label claim. [note—Use this Test solution within 3 hours if stored at room temperature, or within 20 hours when stored under refrigeration. ]
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows.
Time
(minutes)
Solution A
(%)
Solution B
(%)
Elution
0 95 5 equilibration
0–30 95®75 5®25 linear gradient
30–45 75®0 25®100 linear gradient
45–55 0 100 isocratic
55–60 0®95 100®5 reset composition
60–70 95 5 re-equilibration
Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: identify the peaks by their relative retention times, which are about 0.85 and 1.0 for the delta-3 isomer and cefaclor, respectively; the resolution, R, between the delta-3 isomer and cefaclor is not less than 2.0; and the tailing factor for the cefaclor peak is not more than 1.2. Chromatograph the Blank solution as directed for Procedure. Examine the chromatogram for any extraneous peaks, and disregard any corresponding peaks observed in the chromatogram of the Test solution.
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 area responses for all the peaks. Calculate the percentage of each related compound in the portion of Capsules taken by the formula:
100(P)(CS / CU)(ri / rS)
in which P is the potency, in mg of cefaclor, per mg of USP Cefaclor RS; CS is the concentration, in mg per mL, of USP Cefaclor RS in the Standard solution; CU is the nominal concentration, in mg per mL, of cefaclor in the Test solution; ri is the peak response of an individual related compound in the chromatogram obtained from the Test solution; and rS is the peak response for the cefaclor peak in the chromatogram of the Standard solution. The reporting level for impurities is 0.1%. Not more than 0.5% of any individual related compound is found; and the sum of all related compounds is not more than 2.0%.
Assay—
Mobile phase— Dissolve 1 g of sodium 1-pentanesulfonate in a mixture of 780 mL of water and 10 mL of triethylamine. Adjust with phosphoric acid to a pH of 2.5 ± 0.1, add 220 mL of methanol, and mix. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Cefaclor RS in Mobile phase to obtain a solution having a known concentration of about 0.3 mg per mL of cefaclor. Sonicate briefly, if necessary, to achieve dissolution, and avoid heating the solution. [note—Use this Standard preparation within 8 hours if stored at room temperature, or within 20 hours if stored under refrigeration. ]
Assay preparation— Remove, as completely as possible, the contents of not fewer than 20 Capsules, and weigh accurately. Mix the combined contents, and transfer an accurately weighed portion of the powder, equivalent to about 75 mg of cefaclor, to a 250-mL volumetric flask, dilute with Mobile phase to volume, and mix. Sonicate if necessary to ensure complete dissolution of the cefaclor. Filter to obtain the clear Assay preparation. The nominal concentration of this solution is 0.3 mg per mL of cefaclor based on the label claim.
System suitabilty solution— Dissolve accurately weighed quantities of USP Cefaclor RS and USP Cefaclor Delta-3 Isomer RS in Mobile phase to obtain a solution having a known concentration of about 0.3 mg each of cefaclor and the delta-3 isomer per mL.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 265-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the responses as directed for Procedure: identify the peaks by their relative retention times, which are about 0.8 and 1.0 for cefaclor and the delta-3 isomer, respectively; the resolution, R, between the cefaclor peak and the delta-3 isomer peak is not less than 2.5; the tailing factor is not more than 1.5; and the relative standard deviation for replicate injections is not more than 2%.
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 percent label claim of cefaclor (C15H14ClN3O4S) in the portion of Capsules taken by the formula:
(P)(CS / CU)(rU / rS)(100)
in which P is the potency, in mg, of cefaclor (C15H14ClN3O4S) per mg, of USP Cefaclor RS; CS is the concentration, in mg per mL, of USP Cefaclor RS in the Standard preparation; CU is the nominal concentration, in mg per mL, of cefaclor in the Assay preparation; and rU and rS are the peak responses of the cefaclor peaks obtained from the Assay preparation and the Standard preparation, respectively.
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