Paricalcitol Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Paricalcitol Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of paricalcitol (C₂₇H₄₄O₃). They may contain butylated hydroxytoluene or other suitable antioxidant.

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

[Note—Protect paricalcitol solutions from light.]

Solution A: Acetonitrile, isopropyl alcohol, and water (50:15:35)

Solution B: Acetonitrile and isopropyl alcohol (50:50)

Mobile phase: See Table 1.

Table 1

Internal standard solution: 0.75 µg/mL of triphenylene in acetonitrile

Standard stock solution: 10 µg/mL of paricalcitol from USP Paricalcitol Solution RS in acetonitrile

Standard solution: A mixture of 0.5 µg/mL of paricalcitol from Standard stock solution and 0.15 µg/mL of triphenylene from Internal standard solution in acetonitrile

Sample solution: Nominally 0.5 µg/mL of paricalcitol from Capsules and 0.15 µg/mL of triphenylene from Internal standard solution, prepared as follows. Transfer 10 Capsules to a suitable container. Transfer the volume of acetonitrile specified in Table 2 to a separate beaker. Cut each Capsule to allow the oil to flow freely from the shell. Rinse any tools used to open the shells by pouring in portions of acetonitrile from the beaker into the sample container. When the rinsing is complete, add the remainder of the acetonitrile to the sample container, add the volume of Internal standard solution specified in Table 2, and mix well. [Note—To facilitate cutting the Capsules open, soften them in a suitable microwave oven for NMT 10 s; taking care not to melt the Capsules. A microwave oven of 600–825 watts was found to be suitable for this procedure.]

Table 2

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 252 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 2.0 mL/min

Injection volume: 50 µL

Run time: 20 min

3.2 System suitability

Sample: Standard solution

[Note—The relative retention times for paricalcitol and triphenylene are 1.0 and 2.0, respectively.]

Suitability requirements

Resolution: NLT 4.0 between paricalcitol and triphenylene

Tailing factor: NMT 2.0 for the paricalcitol peak

Relative standard deviation: NMT 2.0% for the peak response ratios of paricalcitol to triphenylene

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of paricalcitol (C₂₇H₄₄O₃) in the portion of Capsules taken:

Result = (R_U /R_S ) × (C_S /C_U ) × F × 100

R_U= peak response ratio of paricalcitol to triphenylene from the Sample solution

R_S = peak response ratio of paricalcitol to triphenylene from the Standard solution

C_S = concentration of paricalcitol from USP Paricalcitol Solution RS in the Standard solution (µg/mL)

C_U = nominal concentration of paricalcitol in the Sample solution (µg/mL)

F = internal standard correction factor (see Table 2)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Rupture Test

Apparatus: Disintegration apparatus with mesh wire, as described in Disintegration 〈701〉

Medium: Water

Procedure: Preheat disintegration apparatus water bath to 37 ± 2°. Transfer an appropriate volume of water such that at the highest point of the upward stroke the wire mesh of the basket-rack assembly remains at least 15 mm below the surface of the uid and descends to NLT 25 mm from the bottom of the vessel on the downward stroke. Place the beakers in the water bath and allow the contents to warm to 37 ± 2°; the uid must be maintained at this temperature for the duration of the test. Place one Capsule in each of the six tubes of the basket rack assembly, adding a mesh wire screen to each tube, then start the action of the lifting apparatus and timing simultaneously. Observe the units at 5-min intervals.

Tolerances: The requirements are met if all of the Capsules tested rupture in NMT 15 min.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

[Note—Unless otherwise specified, protect paricalcitol solutions from light.]

Solution A: Water

Solution B: Acetonitrile

Solution C: Acetonitrile and isopropyl alcohol (50:50)

Mobile phase: See Table 3.

Table 3

Diluent: Acetonitrile and water (50:50)

Degradation stock solution: Dilute 1 mL of USP Paricalcitol Solution RS with Diluent to 5 mL.

Degradation solution A: Transfer 1 mL of the Degradation stock solution and 0.1 mL of 30% Hydrogen peroxide to a suitable container, and allow to stand at room temperature for 1 h. Dilute with Diluent to 10 mL, and mix. This solution contains paricalcitol and related compounds A and B.

Degradation solution B: Mix 1 mL of the Degradation stock solution and 1 mL of 0.1 N hydrochloric acid, and heat at 70° for 1 h. Cool to room temperature, dilute with Diluent to 10 mL, and mix. This solution contains paricalcitol and related compounds C, D, G, H, and I. Internal standard solution: 0.08 µg/mL of Calcitriol from USP Calcitriol Solution RS in acetonitrile

Standard solution: 0.01 µg/mL of paricalcitol from USP Paricalcitol Solution RS and 0.016 µg/mL of calcitriol from Internal standard solution in Diluent

Sample solution: Nominally 1.8 µg/mL of paricalcitol from Capsules, prepared as follows. Remove the contents of a suitable number of Capsules using a syringe or cut the Capsules open with scissors and transfer the contents to a suitable container. Transfer a portion of mixed Capsule contents containing nominally 18 µg of paricalcitol to a 10-mL volumetric flask. Add acetonitrile to obtain a total mass of 5 g. Transfer 2.0 mL of Internal standard solution to the flask and dilute with water to volume. Mix using a vortex mixer. Centrifuge for 5-min intervals until the top layer is clear, then transfer the supernatant to a suitable chromatographic vial within 2 min.

5.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 252 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1.5 mL/min

Injection volume: 300 µL

Run time: 55 min

5.2 System suitability

Sample: Standard solution

[Note—The relative retention times for paricalcitol and calcitriol are 1.0 and 1.03, respectively. See Table 4 for all other relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between paricalcitol and calcitriol

Relative standard deviation: NMT 7.0% for the peak response ratio of paricalcitol to calcitriol

5.3 Analysis

Samples: Degradation solution A, Degradation solution B, Standard solution, and Sample solution

Identify the impurities in the Sample solution on the basis of the relative retention times of the components of Degradation solution A and Degradation solution B in Table 4.

Table 4

a Related compounds A, B, C, D, G, H, and I are specified unidentified degradation products. No information is available about chemical structures or chemical names for these impurities.

b (7Z,22E)-19-Nor-9,10-secoergosta-5,7,22-triene-1α,3β,25-triol.

Calculate the percentage of each impurity in the portion of Capsules taken:

Result = (R_U /R_S ) × (C_S /C_U) × 100

R_U = peak response ratio of each impurity to calcitriol from the Sample solution

R_S = peak response ratio of paricalcitol to calcitriol from the Standard solution

C_S = concentration of paricalcitol from USP Paricalcitol Solution RS in the Standard solution (µg/mL)

C_U = nominal concentration of paricalcitol in the Sample solution (µg/mL)

Acceptance criteria

Any individual impurity: NMT 2.0%

Total impurities: NMT 3.0%

6 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉andTests for Specified Microorganisms 〈62〉: The total aerobic microbial count is NMT 10³ cfu/g, and the total combined yeasts and molds count is NMT 102 cfu/g. Meet the requirements of the test for absence of Escherichia coli.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in a tight container. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Calcitriol Solution RS

USP Paricalcitol Solution RS