» Paricalcitol Injection is a sterile solution of Paricalcitol in a mixture of Water for Injection, Propylene Glycol, and Alcohol. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of paricalcitol (C27H44O3). It contains no antimicrobial agents.
Packaging and storage Preserve in single-dose containers, preferably of Type I glass. Store at controlled room temperature.
USP Reference standards 11
USP Endotoxin RS
USP Paricalcitol Solution 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.
Bacterial endotoxins 85 It contains not more than 10 USP Endotoxin Units per µg of paricalcitol.
Particulate matter 788: meets the requirements for small-volume injections.
Limit of aluminum 206
Nitric acid diluent Dilute 4 mL of nitric acid to 2000 mL with water.
Matrix modifier solution Dissolve 1.5 g of magnesium nitrate in 1000 mL of water.
Standard stock solution Proceed as directed in the chapter under Standard Preparations, beginning with Treat some aluminum wire and ending with Cool, and transfer the solution, with the aid of water, to a 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 2 mL of this solution to a second 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 2 mL of this solution to a third 100-mL volumetric flask, dilute with water to volume, and mix. This solution contains about 0.4 µg of aluminum per mL.
Standard solutions Dilute accurately measured portions of the Standard stock solution with Nitric acid diluent to obtain solutions having known concentrations of about 2.5, 5.0, 10, 20, and 50 ng of aluminum per mL.
Test solution Dilute 4.0 mL of Injection with 6.0 mL of Nitric acid diluent or use an appropriate dilution to obtain a solution having a concentration not greater than 0.02 µg of aluminum per mL.
System suitability solution Dilute 9.5 mL of the Test solution with 0.5 mL of the Standard stock solution. If the resulting solution contains more than 0.04 µg of aluminum per mL, prepare an alternate dilution having a concentration between about 0.02 and 0.04 µg of aluminum per mL.
Procedure Concomitantly determine the absorbances of the Standard solutions, the System suitability solution, and the Test solution at the aluminum emission line at 309.3 nm with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering 851) equipped with an aluminum hollow-cathode lamp and a flameless electrically heated furnace. Under typical conditions, the sample volume is 20 µL, the volume of the Matrix modifier solution is 5 µL, the injection temperature is 100, and the oven conditions are as follows [noteThese conditions may be optimized for each instrument ] :
CD,in which C is as defined above; and D is the dilution factor used to prepare the Test solution: not more than 0.5 µg per mL is found.
Diluent Prepare a mixture of water and acetonitrile (1:1).
Solution A Prepare a filtered and degassed mixture of water and acetonitrile (85:15).
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 Prepare a solution of USP Paricalcitol Solution RS in Diluent having a known concentration of paricalcitol equal to about 0.5% of the labeled concentration of the Injection.
Control standard solution Transfer 5.0 mL of the Standard solution to a 25.0-mL volumetric flask, dilute with Diluent to volume, and mix.
Degradation stock solution Accurately dilute about 1 mL of USP Paricalcitol Solution RS with Diluent to 5 mL.
Degradation solution 1 Transfer about 1 mL of the Degradation stock solution and 0.1 mL of 30 percent hydrogen peroxide into a 10-mL container, and allow to stand at room temperature for 1 hour. Dilute with Diluent to 10 mL, and mix.
Degradation solution 2 Place about 1 mL of the Degradation stock solution and 1 mL of 0.1 N hydrochloric acid in a 10-mL container. Mix, and heat at 70 for 1 hour. Cool to room temperature, dilute with Diluent to 10 mL, and mix.
Test solution Use the Injection.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 252-nm detector, a 4.6-mm × 7.5-cm guard column that contains packing L1, 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.
Procedure Chromatograph the Degradation solution 1, and identify the paricalcitol peak and the peaks due to the related compounds listed in Table 1.
100(C/L)(ri / rS)in which C is the concentration, in µg per mL, of paricalcitol in the Standard solution, calculated on the basis of the content of paricalcitol in the USP Paricalcitol Solution RS; L is the labeled amount, in µg per mL, of paricalcitol in the Injection; 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: in addition to not exceeding the limits for impurities in Tables 1 and 2, not more than 2.0% of total impurities is found.
Content of propylene glycol and alcohol
Mobile phase Prepare a filtered and degassed 0.01 N sulfuric acid solution.
Alcohol standard solution Transfer 2.0 mL of dehydrated alcohol to a 10-mL volumetric flask, dilute with water to volume, and mix.
Propylene glycol standard solution Transfer 3.0 mL of propylene glycol to a 10-mL volumetric flask, dilute with water to volume, and mix.
Standard solution Transfer 5.0 mL each of Alcohol standard solution and Propylene glycol standard solution to a 50-mL volumetric flask, dilute with water to volume, and mix.
Test solution Transfer 5.0 mL of the Injection to a 50-mL volumetric flask, dilute with water to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a refractive index detector and a 7.8-mm × 30-cm column that contains packing L17. The column temperature is maintained at 60. The flow rate is about 0.8 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the elution order is propylene glycol followed by alcohol; the resolution, R, between propylene glycol and the alcohol is not less than 4.0; and the relative standard deviation for replicate injections is not more than 2.0% for each peak.
Procedure Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatographs, and measure the responses for the major peaks. Calculate the percentage of propylene glycol and alcohol in the portion of Injection taken by the formula:
C(rU / rS)in which C is the concentration, in percentage, of alcohol or propylene glycol in the Alcohol standard solution or Propylene glycol standard solution, respectively; and rU and rS are the corresponding peak responses obtained from the Test solution and the Standard solution, respectively: between 16% and 24% of dehydrated alcohol is found; and between 26% and 34% of propylene glycol is found.
Other requirements It meets the requirements under Injections 1.
Diluent, Mobile phase, and Chromatographic system Proceed as directed in the Assay under Paricalcitol.
Standard preparation Prepare a solution of USP Paricalcitol Solution RS in Diluent having a known concentration of paricalcitol similar to that of the Injection.
Assay preparation Use the Injection.
Procedure Separately inject equal volumes (about 100 to 200 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 µg, of paricalcitol (C27H44O3) in each mL of the Injection taken by the formula:
C(rU / rS)in which C is the concentration, in µg per mL, of paricalcitol in the Standard preparation, calculated on the basis of the content of paricalcitol in the USP Paricalcitol Solution RS; and rU and rS are the paricalcitol peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 4221Pharmacopeial Forum: Volume No. 29(5) Page 1554