Paricalcitol

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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C₂₇H₄₄O₃       416.64

19-Nor-1-α,25-dihydroxyvitamin D₂;

(1α,3β,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-1α,3β,25-triol CAS RN®: 131918-61-1; UNII: 6702D36OG5.

1 DEFINITION

Paricalcitol contains NLT 97.0% and NMT 103.0% of paricalcitol (C₂₇H₄₄O₃), calculated on the dried basis.

[Caution—Handle 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.]

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

B. 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.]

Mobile phase: Methanol and water (4:1)

Diluent: Methanol and water (1:1)

Standard solution: Dilute USP Paricalcitol Solution RS with Diluent to obtain a solution containing 5.0 µg/mL of paricalcitol. Sample solution: Transfer an accurately weighed amount of Paricalcitol to a suitable volumetric flask, add dehydrated alcohol (approximately 1 mL of dehydrated alcohol per each 0.5 mg of paricalcitol), sonicate to dissolve, and dilute with Diluent to volume. Further dilute this solution with Diluent to obtain a solution containing 5.0 µg/mL of paricalcitol.

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 mL/min

Injection volume: 100 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of paricalcitol (C₂₇H₄₄O₃) in the portion of Paricalcitol taken:

Result = (r_U /r_S ) × (C_S /C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of paricalcitol in the Standard solution (µg/mL)

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

Acceptance criteria: 97.0%–103.0% on the dried basis

4 IMPURITIES

Organic Impurities

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

Diluent: Dehydrated alcohol and water (50:50)

Solution A: Acetonitrile and water (5:95)

Solution B: Acetonitrile and methanol (75:25)

Mobile phase: See Table 1.

Table 1

a Determine the retention time of the paricalcitol peak using the Standard solution. Adjust the start of the gradient to be 1.0 ± 0.1 min prior to the retention time of paricalcitol and accordingly adjust the remaining gradient times.

System suitability stock solution: Prepare a 50-µg/mL solution of paricalcitol from USP Paricalcitol Solution RS in dehydrated alcohol. Using a colorless glass container, expose the solution to ultraviolet light at 254 nm. Paricalcitol undergoes partial degradation to 7Z-paricalcitol. A degradation of at least 0.2% of paricalcitol to 7Z-paricalcitol [(7Z,22E)-19-nor-9,10-secoergosta-5,7,22-triene-1α,3β,25-triol] must be obtained, based on the corresponding peaks. If it is not obtained, expose the solution to ultraviolet light again.

System suitability solution: System suitability stock solution and water (1:1)

Standard stock solution: 5 µg/mL of paricalcitol from USP Paricalcitol Solution RS in Diluent

Standard solution: 0.15 µg/mL of paricalcitol from Standard stock solution in Diluent

Sensitivity solution: 0.05 µg/mL of paricalcitol from Standard solution in Diluent

Sample stock solution: 200 µg/mL of Paricalcitol in dehydrated alcohol

Sample solution: 100 µg/mL of Paricalcitol from Sample stock solution in water

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 252 nm

Column: 4.6-mm × 10-cm; 2.7-µm packing L1

Column temperature: 30°

Flow rate: 0.9 mL/min

4.2 System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[Note—The relative retention times for paricalcitol and 7Z-paricalcitol are 1.0 and 1.06, respectively.]

Suitability requirements

Resolution: NLT 1.5 between paricalcitol and 7Z-paricalcitol, System suitability solution Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

4.3 Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U /r_S ) × (C_S /C_U) × (1/F) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of paricalcitol from the Standard solution

C_S = concentration of paricalcitol in the Standard solution (µg/mL)

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard peaks less than 0.05%.

Table 2

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

5 SPECIFIC TESTS

Loss on Drying

(See Thermal Analysis 〈891〉.)

Sample: 8 mg of Paricalcitol

Analysis: Determine the percentage of volatile substances by thermogravimetric analysis on an appropriately calibrated instrument. Heat at a rate of 5°/min between ambient temperature and 150° in an atmosphere of nitrogen at a ow rate of 40 mL/min. Determine the accumulated loss in weight from the thermogram.

Acceptance criteria: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, and store under argon in a freezer.

USP Reference Standards 〈11〉

USP Paricalcitol RS

USP Paricalcitol Solution RS