Primaquine Phosphate Tablets

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

Primaquine Phosphate Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of primaquine phosphate (C₁₅H₂₁N₃O·2H₃PO₄).

2 IDENTIFICATION

Change to read:

A. ▲The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲ (USP 1-Aug-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

Change to read:

Procedure

Mobile phase: Acetonitrile, tetrahydrofuran, trifluoroacetic acid, and water (9:1:0.1:90)

Standard solution: 0.4 mg/mL of USP Primaquine Phosphate RS in Mobile phase. Sonicate with intermittent shaking to dissolve, if necessary.

System suitability stock solution: 0.4 mg/mL of USP Primaquine Related Compound A RS in Mobile phase

System suitability solution: Transfer 1.0 mL of System suitability stock solution to a 10-mL volumetric flask, and dilute with Standard solution to volume.

Sensitivity solution: 0.2 µg/mL of USP Primaquine Phosphate RS from Standard solution ▲in Mobile phase▲ (USP 1-Aug-2020)

Sample stock solution: Transfer a quantity of Tablets (NLT 20), accurately counted and weighed, to a 500-mL volumetric flask. Add 300 mL of Mobile phase, then sonicate and shake for 15 min. Add 150 mL of Mobile phase, then sonicate and shake for 15 min. Dilute with Mobile phase to volume, and filter.

Sample solution: ▲Nominally▲ (USP 1-Aug-2020) 0.4 mg/mL of primaquine phosphate in Mobile phase from the Sample stock solution

Chromatographic system
(See Chromatography 〈621〉, System Suitability.)

Mode: LC
Detector: UV 265 nm. ▲For Identification A, use a diode array detector in the range of 220–400 nm.▲ (USP 1-Aug-2020)
Column: 4.6-mm × 75-mm; 3-µm packing L7
Flow rate: 1.5 mL/min
Injection volume: 10 µL
Run time: ▲NLT▲ (USP 1-Aug-2020) 3 times the retention time of primaquine

System suitability

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

Suitability requirements

Resolution: NLT 2.5 between primaquine phosphate and primaquine related compound A, System suitability solution

Relative standard deviation: NMT 1.0% for primaquine phosphate, Standard solution

Signal-to-noise ratio: NLT 10 for the primaquine peak, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of primaquine phosphate (C₁₅H₂₁N₃O·2H₃PO₄) in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response from the Sample solution
rₛ = peak response from the Standard solution
Cₛ = concentration of USP Primaquine Phosphate RS in the Standard solution (mg/mL)
Cᵤ = nominal concentration of primaquine phosphate in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–107.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Medium: 0.01 N hydrochloric acid; 900 mL
Apparatus 2: 50 rpm
Time: 60 min

Solution A: 961 mg of sodium 1-pentanesulfonate and 1 mL of glacial acetic acid in 400 mL of water

Mobile phase: Methanol and Solution A (3:2)

Sample solution: Pass a portion of the solution under test through an appropriate filter.

Standard solution: USP Primaquine Phosphate RS in Medium in a concentration similar that of the Sample solution

Chromatographic system
(See Chromatography 〈621〉, System Suitability.)

Mode: LC
Detector: UV 254 nm
Column: 3.9-mm × 30-cm; packing L1
Flow rate: 2 mL/min
Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 3.0%

Analysis

Samples: Sample solution and Standard solution

Calculate the ▲percentage of the labeled▲ (USP 1-Aug-2020) amount of primaquine phosphate (C₁₅H₂₁N₃O·2H₃PO₄) dissolved:

▲Result = (rᵤ / rₛ) × (C / L) × V × D × 100

rᵤ = peak response of primaquine from the Sample solution
rₛ = peak response of primaquine from the Standard solution
C = concentration of USP Primaquine Phosphate RS in the Standard solution (mg/mL)
L = label claim (mg/Tablet)
V = volume of Medium, 900 mL
D = dilution factor for the Sample solution, if applicable▲ (USP 1-Aug-2020)

Tolerances: NLT 80% (Q) of the labeled amount of primaquine phosphate (C₁₅H₂₁N₃O·2H₃PO₄) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

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Organic Impurities

Mobile phase, Standard solution, System suitability solution, Sensitivity solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

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

Result = (rᵢ / rₜ) × 100

rᵢ = peak response of each impurity from the Sample solution
rₜ = peak response of primaquine phosphate from the Sample solution

Acceptance criteria: See Table 1.

[Note—▲The reporting threshold is▲ (USP 1-Aug-2020) 0.05%.]

ᵃ These process impurities are listed for information only and are not quantified in the drug product.

ᵇ 6-Methoxyquinolin-8-amine.

ᶜ 2,3-Dihydrophthalazine-1,4-dione.

ᵈ 8-[(4-Aminopentyl)amino]-6-methoxyquinoline.

ᵉ N³-(6-Methoxyquinolin-8-yl)pentane-1,3-diamine.

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in well-closed, light-resistant containers ▲at controlled room temperature.▲ (USP 1-Aug-2020)

USP Reference Standards 〈11〉

USP Primaquine Phosphate RS

USP Primaquine Related Compound A RS

8-[(4-Aminopentyl)amino]-6-methoxyquinoline.

C₁₅H₂₁N₃O 259.35