Paricalcitol
19-Nor-1-,25-dihydroxyvitamin D2. (1,3,7E,22E)-19-Nor-9,10-secoergosta-5,7,22-triene-1,3,25-triol. (7E,22E)-19-Nor-9,10-secoergosta-5,7,22-triene-1,3,25-triol [131918-61-1]. » Paricalcitol contains not less than 97.0 percent and not more than 103.0 percent of C27H44O3, calculated on the dried basis.
CautionHandle Paricalcitol with exceptional care because it is very potent. Care should be taken to prevent inhaling particles of Paricalcitol and exposing the skin to it.
Packaging and storage
Preserve in tight, light-resistant containers, and store under argon in a freezer.
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.
Loss on drying (see Thermal Analysis 891)
Determine the percentage of volatile substances by thermogravimetric analysis on an appropriately calibrated instrument, using about 8 mg of Paricalcitol, accurately weighed. Heat at a rate of 5 per minute between ambient temperature and 150 in an atmosphere of nitrogen at a flow rate of 40 mL per minute. From the thermogram determine the accumulated loss in weight: it loses not more than 2.0% of its weight.
Chromatographic purity
[noteUse low-actinic glassware to prepare solutions of Paricalcitol.]
Diluent
Prepare a mixture of water and dehydrated alcohol (1:1).
Butylparaben solution
Transfer about 25 mg of butylparaben to a 100-mL volumetric flask, dilute with Diluent to volume, and mix.
Solution A
Use a filtered and degassed mixture of water and acetonitrile (95:5), and add 1 drop of phosphoric acid per L of solution.
Solution B
Use filtered and degassed acetonitrile.
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).
Standard solution
Dilute USP Paricalcitol Solution RS in Diluent to a known concentration of about 0.1 µg of paricalcitol per mL.
Control standard solution
Transfer 3.0 mL of the Standard solution to a 10.0-mL volumetric flask, dilute with Diluent to volume, and mix.
Test stock solution
Prepare a solution of Paricalcitol in dehydrated alcohol, having a known concentration of about 200 µg per mL.
Resolution solution
Transfer 1 mL of the Butylparaben solution and 1 mL of the Test stock solution to a 100-mL volumetric flask, dilute with Diluent to volume, and mix. Transfer 1 mL of this solution to a 10-mL volumetric flask, dilute with Diluent to volume, and mix.
Test solution
Prepare a mixture of the Test stock solution and water (1:1).
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 252-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 2 mL per minute. The chromatograph is programmed as follows.
Procedure
Separately inject equal volumes (about 100 µL) of the Diluent, the Standard solution, and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses, disregarding any peaks corresponding to those obtained from the Diluent. Calculate the percentage of each impurity in the portion of Paricalcitol taken by the formula:
100(CS / CU)(ri / rS)
in which CS and CU are the concentrations, in µg per mL, of paricalcitol in the Standard solution and the Test solution, respectively; ri is the peak response for each impurity obtained from the Test solution; and rS is the paricalcitol peak response obtained from the Standard solution: not more than 0.1% of any individual impurity is found; and not more than 0.5% of total impurities is found.
Assay
[noteUse low-actinic glassware to prepare solutions of paricalcitol.]
Mobile phase
Prepare a filtered and degassed mixture of methanol and water (4:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent
Prepare a mixture of methanol and water (1:1).
Standard preparation
Transfer an accurately weighed amount of USP Paricalcitol RS to a suitable volumetric flask, dissolve in a minimum amount of dehydrated alcohol, and dilute with Diluent to volume. Further dilute this solution quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 5.0 µg per mL.
Assay preparation
Transfer an accurately weighed amount of Paricalcitol to a suitable volumetric flask, dissolve in a minimum amount of dehydrated alcohol, and dilute with Diluent to volume. Further dilute this solution quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 5.0 µg per mL.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 252-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure
Separately inject equal volumes (about 100 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 C27H44O3 in the portion of Paricalcitol taken by the formula:
100(CS / CU)(rU / rS)
in which CU and CS are the concentrations, in µg per mL, of paricalcitol in the Assay preparation and the Standard preparation, respectively; and rU and rS are the paricalcitol peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 3210
Pharmacopeial Forum: Volume No. 33(2) Page 252
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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