Altretamine 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

Altretamine Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of altretamine (C₉H₁₈N₆).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

Sample: Remove as completely as possible the contents of 5 Capsules, and dissolve, with shaking, in 10 mL of chloroform. Filter, and evaporate the chloroform solution to dryness.

Acceptance criteria: Meet the requirements

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:

3.1 PROCEDURE

Solution A: 1.7 g/L of dibasic potassium phosphate in water. Adjust with phosphoric acid to a a pH of 7.0 ± 0.1.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard stock solution: 1.0 mg/mL of USP Altretamine RS prepared as follows. Dissolve a suitable amount of USP Altretamine RS in about 40% of the flask volume of acetonitrile. Sonicate as needed to dissolve. Add water almost to volume and allow it to reach room temperature. Dilute with water to volume and mix.

Standard solution: 0.1 mg/mL of USP Altretamine RS in water from Standard stock solution

Sample stock solution: Nominally 1.0 mg/mL of altretamine from Capsules prepared as follows. Transfer NLT 20 Capsules to a suitable volumetric flask. Dissolve in about 40% of the flask volume of acetonitrile. Sonicate as needed to dissolve. Add water almost to volume and allow the solution to reach room temperature. Dilute with water to volume and mix.

Sample solution: Nominally 0.1 mg/mL of altretamine in water from Sample stock solution

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 242 nm

Column: 4.6-mm × 25-cm; 5-µm packing L96

Flow rate: 1.5 mL/min

Injection volume: 20 µL. [NOTE-In-line filter may be needed to reduce system pressure.] (USP 1-May-2019)

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of altretamine (CHN) in the portion of Capsules taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

Add the following:

ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Standard solution, and Sample solution: Prepare as directed in the Assay.

Sensitivity solution: 0.1 µg/mL of USP Altretamine RS in water from Standard solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 and 242 nm (see Table 2)

Column: 4.6-mm x 25-cm; 5-µm packing L96

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Samples: Standard solution and Sensitivity solution

Suitability requirements

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of altretamine from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is NMT 0.1%.

Table 2

^a 6-(Dimethylamino)-1,3,5-triazine-2,4[1H,3H]-dione.

^b 4-Chloro-6-(dimethylamino)-1,3,5-triazine-2[1H]-one.

^c 4,6-Bis(dimethylamino)-1,3,5-triazine-2[1H]-one.

^d 4,6-Dichloro-N,N-dimethyl-1,3,5-triazine-2-amine.

^e 6-Chloro-N²,N²,N⁴,N⁴-tetramethyl-1,3,5-triazine-2,4-diamine.

^f Use the detector consistent with the respective impurity.

5 PERFORMANCE TESTS

5.1 DISSOLUTION (711)

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Detector: UV 242 nm

Standard solution: USP Altretamine RS in Medium

Analysis: Determine the amount of altretamine (C₉H₁₈N₆) dissolved from UV absorbances on filtered portions of the solution under test, suitably diluted if necessary with Medium, compared with the Standard solution.

Tolerances: NLT 80% (Q) of the labeled amount of altretamine (C₉H₁₈N₆) is dissolved.

5.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers, and store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Altretamine RS