» Methoxsalen Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of methoxsalen (C12H8O4).
Packaging and storage Preserve in tight, light-resistant containers.
Labeling Label the Capsules to state that Methoxsalen Hard Gelatin Capsules may not be interchangeable with Methoxsalen Soft Gelatin Capsules without retitration of the patient.
USP Reference standards 11
A: The retention time exhibited by methoxsalen in the chromatogram of the Assay preparation corresponds to that of methoxsalen in the chromatogram of the Standard preparation as obtained in the Assay.
B: Place one Capsule in 50 mL of alcohol contained in a high-speed glass blender jar and blend thoroughly until the shell is completely dispersed. Dilute a portion quantitatively with alcohol to obtain a solution having a concentration of about 4 µg per mL: the UV absorption spectrum of the solution so obtained exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Methoxsalen RS, concomitantly measured.
For soft gelatin capsules
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Time: 45 minutes.
Procedure Determine the amount of C12H8O4 dissolved from UV absorbances at the wavelength of maximum absorbance at about 300 nm using filtered portions of the solution under test, suitably diluted with water, if necessary, in comparison with a Standard solution having a known concentration of USP Methoxsalen RS in the same Medium. [noteAn amount of alcohol not to exceed 1% of the total volume of the Standard solution may be used to bring the Reference Standard into solution prior to dilution with Medium. ]
Tolerances Not less than 75% (Q) of the labeled amount of C12H8O4 is dissolved in 45 minutes.
for hard gelatin capsules
Medium: water; 900 mL.
Apparatus 1: 150 rpm.
Time: 90 minutes.
Procedure Determine the amount of C12H8O4 dissolved from UV absorbances at the wavelength of maximum absorbances at about 252 nm of filtered portions of the solution under test in comparison with a Standard solution having a known concentration of USP Methoxsalen RS prepared in alcohol and diluted with water.
Tolerances Not less than 75% (Q) of the labeled amount of C12H8O4 is dissolved in 90 minutes.
Uniformity of dosage units 905: meet the requirements.
Mobile phase Prepare a filtered and degassed mixture of acetonitrile and water (65:35). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Prepare a solution in alcohol having an accurately known concentration of 0.2 mg of USP Methoxsalen RS per mL. Pipet 2.0 mL of this solution into a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
for hard gelatin capsules Place not less than 10 Capsules in a high-speed glass blender jar containing 100.0 mL of alcohol, and blend thoroughly. Transfer an accurately measured volume of the aliquot from the blender jar, equivalent to about 2 mg of Methoxsalen, to a 50-mL volumetric flask, dilute with alcohol to volume, mix, and filter. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, mix, and filter.
for soft gelatin capsules Place the end of a long-stem glass funnel on a 250-mL volumetric flask, punch a hole at each end of a Capsule with a syringe containing 15 mL of alcohol, and rinse the contents into the flask. Cut the Capsule shell with a scalpel, and wash the inside of the shell with 15 mL of alcohol into the same flask. Repeat these steps for not less than 4 additional Capsules, and collect the rinse. Wash the funnel, and collect the rinse in the same flask. Dilute with alcohol to volume, and mix. Transfer an accurately measured volume of this solution, equivalent to about 2 mg of methoxsalen, to a 50-mL volumetric flask, dilute with alcohol to volume, mix, and filter. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, mix, and filter.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 254-nm detector and a 4-mm × 30-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. 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 responses for the major peaks. Calculate the quantity, in percentage of the label claim, of methoxsalen (C12H8O4) in the portion of the Capsule taken by the formula:
100(CS / CU)(rU / rS)in which CS is the concentration, in mg per mL, of USP Methoxsalen RS in the Standard preparation; CU is the nominal concentration, in mg per mL, of methoxsalen in the Assay preparation, based on the label claim; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3860Pharmacopeial Forum: Volume No. 34(1) Page 101