Thioguanine Tablets

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

Thioguanine Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of thioguanine (C₅H₅N₅S).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K. (CN 1-May-2020) Record the spectra over the range from 3000 cm^-1 to 650 cm^-1

Sample: Shake a portion of the powdered Tablets equivalent to 0.5 g of thioguanine with 10 mL of 1 M sodium hydroxide, and filter. Acidify the filtrate with hydrochloric acid, filter, and dissolve the precipitate in 25% ammonia water. Evaporate to dryness, and dry the residue at 105° at a pressure not exceeding 0.1 psi for 5 h.

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

Mobile phase: 6 g/L of anhydrous monobasic sodium phosphate in water adjusted with phosphoric acid to a pH of 3.0

Diluent: 0.01 M sodium hydroxide

Standard stock solution: 0.4 mg/mL of USP Thioguanine RS in Diluent

Standard solution: 0.04 mg/mL of USP Thioguanine RS in Mobile phase from the Standard stock solution

Sample stock solution: Nominally 0.4 mg/mL of thioguanine in Diluent prepared as follows. Transfer NLT 20 finely powdered Tablets, equivalent to 40 mg of thioguanine, to a 100-mL volumetric flask. Add 70 mL of Diluent, and shake for 15 min. Dilute with Diluent to volume.

Sample solution: 0.04 mg/mL of thioguanine in Mobile phase from the Sample stock solution. Pass a portion of this solution through a suitable filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 248 nm

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

Flow rate: 2 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of thioguanine (C₅H₅N₅S) in the portion of Tablets 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 thioguanine in the Standard solution (mg/mL)

C_U = nominal concentration of thioguanine in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–107.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Sample solution: Pass a portion of the solution under test through a suitable filter. Transfer 2 mL of the filtrate and 2 mL of 1 M hydrochloric acid to a 20-mL volumetric flask, and dilute with water to volume.

Standard solution: USP Thioguanine RS in 0.1 M hydrochloric acid with a concentration similar to the Sample solution

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 348 nm

Blank: 0.1 M hydrochloric acid

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of thioguanine dissolved:

Result = (A_U/A_S) × C_S × V × D × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of the Medium, 900 mL

D = dilution factor for Sample solution, 10

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of thioguanine is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Diluent: 0.01 M sodium hydroxide

System suitability stock solution: 0.4 mg/mL each of USP Thioguanine RS and USP Guanine RS in 10% (v/v) phosphoric acid. Sonicate to dissolve.

System suitability solution: 0.04 mg/mL each of USP Thioguanine RS and USP Guanine RS in Mobile phase from the System suitability stock solution

Standard stock solution: 8 μg/mL of USP Thioguanine RS and 0.16 mg/mL of USP Guanine RS in Diluent

Standard solution: 0.8 μg/mL of USP Thioguanine RS and 0.016 mg/mL of USP Guanine RS in Mobile phase from the Standard stock solution

Sample solution: Nominally 0.4 mg/mL of thioguanine prepared as follows. Transfer NLT 20 finely powdered Tablets, equivalent to 40 mg of thioguanine, to a 100-mL volumetric flask. Add 10 mL of Diluent, and sonicate for 5 min. Dilute with Mobile phase to volume. Pass a portion of this solution through a suitable filter.

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 3.0 between the thioguanine and guanine peaks, System suitability solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of guanine in the portion of Tablets 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 USP Guanine RS in the Standard solution (mg/mL)

C_U = nominal concentration of thioguanine in the Sample solution (mg/mL)

Calculate the percentage of any individual unspecified impurity in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each unspecified impurity from the Sample solution

r_S = peak response of thioguanine from the Standard solution

C_S = concentration of USP Thioguanine RS in the Standard solution (mg/mL)

C_U = nominal concentration of thioguanine in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. Disregard any impurity peak less than 0.1%.

Table 1

^a 2-Amino-1,7-dihydro-6H-purin-6-one.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at 15°–25°.

USP Reference Standards 〈11〉

USP Guanine RS

2-Amino-1,7-dihydro-6H-purin-6-one.