Thiotepa for Injection

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

Thiotepa for Injection contains NLT 95.0% and NMT 110.0% of the labeled amount of thiotepa.

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

Buffer: 13.6 g/L of monobasic potassium phosphate in water. Adjust with 35 g/L of dibasic sodium phosphate in water to a pH of 7.0.

Mobile phase: Acetonitrile and Buffer (13:87)

System suitability solution: Transfer 10 mg of USP Thiotepa RS to a 4-mL vial, add 2 mL of methanol, and mix. Add 50 μL of 0.1% phosphoric acid solution. Place a cap on the vial, and heat at 65° for 50 s. Cool the solution, add 1 mL of methanol, and mix. [Note—The preparation generates methoxythiotepa.]

Standard solution: 1.5 mg/mL of USP Thiotepa RS in water

Sample solution: Nominally 1.5 mg/mL of thiotepa in water from Thiotepa for Injection

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for thiotepa and methoxythiotepa are about 1.0 and 1.3, respectively.]

Suitability requirements

Resolution: NLT 3 between methoxythiotepa and thiotepa, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of thiotepa in the portion of Thiotepa for Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of thiotepa from the Sample solution

r_S = peak response of thiotepa from the Standard solution

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

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

Acceptance criteria: 95.0%–110.0%

4 IMPURITIES

Organic Impurities

Buffer, Mobile phase, and System suitability solution: Proceed as directed in the Assay.

Peak identification solution: Dissolve 15 mg of USP Thiotepa RS in 10 mL of water, add 1 g of sodium chloride, boil in a water bath for 10 min, and cool. [Note—The preparation generates thiotepa chloroethyl analog.]

Standard solution: 3.75 μg/mL of USP Thiotepa RS in water

Sample solution: Nominally 3.75 mg/mL of thiotepa in water from Thiotepa for Injection. Pass through a suitable filter, and use the filtrate.

Chromatographic system: Proceed as directed in the Assay. In addition, the run time is NLT 4 times the retention time of the thiotepa peak.

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 3 between methoxythiotepa and thiotepa

Analysis

Samples: Peak identi

cation solution, Standard solution, and Sample solution

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

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of thiotepa from the Standard solution

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

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

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

Table 1

^a P,P-Bis(aziridin-1-yl)-N-(2-chloroethyl)phosphinothioic amide.

^b The impurity thiotepa chloroethyl analog is excluded.

5 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

6 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: NMT 6.25 USP Endotoxin Units/mg of thiotepa

Sterility Tests 〈71〉: Meets the requirements

pH 〈791〉

Sample solution: 10 mg/mL of thiotepa constituted as directed in the labeling

Acceptance criteria: 5.5–7.5

Injections and Implanted Drug Products 〈1〉, Product Quality Tests Common to Parenteral Dosage Forms, Specific Tests, Completeness and clarity of solutions: At the time of use, it meets the requirements.

Other Requirements: It meets the requirements in Labeling 〈7〉, Labels and Labeling for Injectable Products.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for constitution, and store in a refrigerator, protected from light.

USP Reference Standards 〈11〉

USP Thiotepa RS