Paricalcitol Injection

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Paricalcitol Injection is a sterile solution of Paricalcitol in a mixture of Water for Injection, Propylene Glycol, and Alcohol, or other suitable solvents. It contains NLT 90.0% and NMT 110.0% of the labeled amount of paricalcitol (C₂₇H₄₄O₃).

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.]

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 having a concentration of paricalcitol similar to that of the Injection.

Sample solution: Use the Injection.

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: 100–200 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of paricalcitol (C₂₇H₄₄O₃) in the portion of Injection 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, calculated on the basis of the content of paricalcitol in the USP Paricalcitol Solution RS (µg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 OTHER COMPONENTS

Content of Propylene Glycol and Alcohol (if present)

Mobile phase: 0.01 N sulfuric acid solution, filtered and degassed

Alcohol stock solution: Transfer 2.0 mL of dehydrated alcohol to a 10-mL volumetric flask, and dilute with water to volume.

Propylene glycol stock solution: Transfer 3.0 mL of propylene glycol to a 10-mL volumetric flask, and dilute with water to volume. Standard solution: Transfer 5.0 mL each of Alcohol stock solution and Propylene glycol stock solution to a 50-mL volumetric flask, and dilute with water to volume.

Sample solution: Transfer 5.0 mL of Injection to a 50-mL volumetric flask, and dilute with water to volume.

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Refractive index

Column: 7.8-mm × 30-cm; packing L17

Column temperature: 60°

Flow rate: 0.8 mL/min

Injection volume: 10 µL

4.2 System suitability

Sample: Standard solution

[Note—Elution order is propylene glycol followed by alcohol.]

Suitability requirements

Resolution: NLT 4.0 between propylene glycol and alcohol

Relative standard deviation: NMT 2.0% for each peak

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amounts of propylene glycol and alcohol in the portion of Injection taken:

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

r_U = peak response of alcohol or propylene glycol from the Sample solution

r_S = peak response of alcohol or propylene glycol from the Standard solution

C_S = concentration of alcohol or propylene glycol in the Alcohol stock solution or Propylene glycol stock solution (% v/v) 

C_U = nominal concentration of alcohol or propylene glycol (if present) in the Injection (% v/v)

Acceptance criteria

Alcohol: 80.0%–120.0%

Propylene glycol: 80.0%–120.0%

5 IMPURITIES

5.1 Aluminum 〈206〉

Diluent: Dilute 4 mL of nitric acid with water to 2000 mL.

Matrix modifier: 1.5 mg/mL of magnesium nitrate

Standard stock solution: Proceed as directed for Standard preparations in the chapter, 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, and dilute with water to volume”. Transfer 2 mL of this solution to a second 100-mL volumetric flask, and dilute with water to volume. Transfer 2 mL of this solution to a third 100-mL volumetric flask, and dilute with water to volume. This solution contains 0.4 µg/mL of aluminum.

Standard solution A: 2.5 ng/mL of aluminum in Diluent, from the Standard stock solution

Standard solution B: 5.0 ng/mL of aluminum in Diluent, from the Standard stock solution

Standard solution C: 10 ng/mL of aluminum in Diluent, from the Standard stock solution

Standard solution D: 20 ng/mL of aluminum in Diluent, from the Standard stock solution

Standard solution E: 50 ng/mL of aluminum in Diluent, from the Standard stock solution

Sample solution: Dilute 4.0 mL of Injection with 6.0 mL of Diluent, or use an appropriate dilution to obtain a solution having a concentration of NMT 0.02 µg/mL of aluminum.

System suitability solution: Dilute 9.5 mL of the Sample solution with 0.5 mL of the Standard stock solution. If the resulting solution contains more than 0.04 µg/mL of aluminum, prepare an alternate dilution having a concentration of about 0.02–0.04 µg/mL of aluminum.

5.1.1 Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic absorption spectrophotometry; instrument equipped with a flameless, electrically heated furnace

Lamp: Aluminum hollow-cathode

Analytical wavelength: Aluminum emission line at 309.3 nm

5.1.2 Analysis

Samples: Standard solution A, Standard solution B, Standard solution C, Standard solution D, Standard solution E, Sample solution, and System suitability solution

Under typical conditions, the sample volume is 20 µL, the volume of the Matrix modifier is 5 µL, the injection temperature is 100°, and the oven conditions are as listed in Table 1. [Note—These conditions may be optimized for each instrument.]

Table 1

Determine the absorbances of the samples. Plot the absorbances of the Standard solutions versus the content of aluminum, in ng/mL, drawing a straight line best fitting the ve points. The correlation coefficient is NLT 0.995, the recovery for the System suitability solution is 80%–120%, and the duplicate injections must agree within 0.0024 µg/mL. From the graph so obtained, determine the quantity of aluminum, C, in µg, found in each mL of the Sample solution.

Calculate the quantity, in µg/mL, of aluminum in the portion of Injection taken:

Result = C × D

C = measured concentration of aluminum in the Sample solution (µg/mL)

D = dilution factor used to prepare the Sample solution

Acceptance criteria: NMT 0.5 µg/mL

5.2 Organic Impurities

Diluent: Acetonitrile and water (1:1)

Solution A: Acetonitrile and water (15:85)

Solution B: Acetonitrile

Mobile phase: See Table 2.

Table 2

Return to the original conditions, and re-equilibrate the system.

Standard solution: Dilute USP Paricalcitol Solution RS with Diluent to obtain a solution having a concentration of paricalcitol equal to 0.5% of the labeled concentration of the Injection.

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 into a 10-mL container, and allow to stand at room temperature for 1 h. Dilute with Diluent to 10 mL, and mix.

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.

Sample solution: Use the Injection.

5.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 252 nm

Columns

Guard: 4.6-mm × 7.5-mm or 4.6-mm × 10-mm; packing L1

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

Flow rate: 1 mL/min

Injection volume: 100–200 µL

5.2.2 System suitability

Samples: Standard solution and Degradation solution B

Suitability requirements

Resolution: NLT 1.0 between the paricalcitol peak and the related compound D peak, Degradation solution B

Relative standard deviation: NMT 5.0%, Standard solution

5.2.3 Analysis

Samples: Diluent, 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 3.

Table 3

a Related compounds A–I are specified unidentified degradation products. No information is available about chemical structures or chemical names for these impurities.

b This peak is very small; the signal-to-noise ratio is approximately 3–5.

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

Result = (r_U /r_S ) × C_S × (100/L)

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, calculated on the basis of the content of paricalcitol in the USP Paricalcitol Solution RS (µg/mL)

L = labeled amount of paricalcitol in the Injection (µg/mL)

Acceptance criteria: See Table 3. Disregard any peak observed in the Diluent.

6 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: It contains NMT 10 USP Endotoxin Units/µg of paricalcitol.

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections

Other Requirements: It meets the requirements under Injections and Implanted Drug Products 〈1〉.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multi-dose containers, preferably of Type I glass. Store at controlled room temperature. 

USP Reference Standards 〈11〉

USP Paricalcitol Solution RS