Bisoctrizole

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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C₄₁H₅₀N₆O₂  658.87

Phenol, 2,2'-methylenebis[6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)]-;

2,2'-Methylenebis[6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol] CAS RN^®: 103597-45-1; UNII: 8NT850TOYS.

1 DEFINITION

Bisoctrizole contains NLT 96.0% and NMT 102.0% of bisoctrizole (C₄₁H₅₀N₆O₂), calculated on the as-is basis.

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

3.1 PROCEDURE

Diluent: Tetrahydrofuran and 0.2% (w/v) aqueous solution of 1-pentane sulfonic acid sodium salt (60:40)

Solution A: 0.4 g of 1-pentane sulfonic acid sodium salt, 800 mL of methanol, 200 mL of water, and 0.5 mL of phosphoric acid

Solution B: 0.4 g of 1-pentane sulfonic acid sodium salt, 1000 mL of methanol, and 0.5 mL of phosphoric acid

Mobile phase: See Table 1. Return to original conditions and re-equilibrate the system.

Table 1

System suitability solution: 0.8 mg/mL of bisoctrizole from USP Bisoctrizole Resolution Mixture RS prepared as follows. Transfer USP Bisoctrizole Resolution Mixture RS to a suitable volumetric flask, dissolve in tetrahydrofuran, and dilute with Diluent to volume.

Standard solution: 0.8 mg/mL of USP Bisoctrizole RS prepared as follows. Transfer USP Bisoctrizole RS to a suitable volumetric flask, dissolve in tetrahydrofuran equivalent to 60% of the final volume, and dilute with Diluent to volume.

Sample solution: Transfer 80 mg of Bisoctrizole to a 100-mL volumetric flask. Dissolve in 60 mL of tetrahydrofuran, and dilute with Diluent to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 346 nm

Column: 3.0-mm × 25-cm; 5-um packing L1

Column temperature: 40°

Flow rate: 0.8 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 2 for the relative retention times for bisoctrizole and the bisoctrizole isomer.]

Suitability requirements

Resolution: NLT 1.5 between bisoctrizole and the bisoctrizole isomer, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of bisoctrizole (C₄₁H₅₀N₆O₂) in the portion of Bisoctrizole 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 s

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

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

Acceptance criteria: 96.0%-102.0% on the as-is basis

4 IMPURITIES

4.1 LIMIT OF BISOCTRIZOLE RELATED COMPOUND A AND BISOCTRIZOLE ISOMER

Diluent, Solution A, Solution B, Mobile phase, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard stock solution A: 0.65 mg/mL of USP Bisoctrizole RS in tetrahydrofuran

Standard stock solution B: 0.40 mg/mL of USP Bisoctrizole Related Compound A RS in tetrahydrofuran

Standard solution: Transfer 5 mL of Standard stock solution A and 1.0 mL of Standard stock solution B to a 100-mL volumetric flask. Add 60 mL of tetrahydrofuran, and dilute with Diluent to volume.

System suitability

Sample: System suitability solution

[NOTE-See Table 2 for the relative retention times for bisoctrizole related compound A and the bisoctrizole isomer.]

Suitability requirements

Resolution: NLT 1.5 between bisoctrizole and the bisoctrizole isomer

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of bisoctrizole related compound A in the portion of Bisoctrizole taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of bisoctrizole related compound A from the Sample solution

r_S = peak response of bisoctrizole related compound A from the Standard solution

C_S = concentration of USP Bisoctrizole Related Compound A RS in the Standard solution (mg/mL)

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

Calculate the percentage of bisoctrizole isomer in the portion of Bisoctrizole taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of bisoctrizole isomer from the Sample solution

r_S = peak response of bisoctrizole from the Standard solution

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

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

Acceptance criteria: See Table 2.

4.2 ORGANIC IMPURITIES

Diluent, Solution A, Solution B, Mobile phase, Standard solution, Sample solution, Chromatographic system, and System

suitability: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

Calculate the percentage of each individual unspecified impurity in the portion of Bisoctrizole taken:

Result = (r_U/r_T) x 100

r_U = peak response of each individual impurity

r_T = sum of the responses of all the peaks

Acceptance criteria: See Table 2.

Table 2

^a 2-(2H-Benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl) phenol.

^b Phenol, 2,2′-methylenebis[6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)]

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Bisoctrizole RS

USP Bisoctrizole Related Compound A RS

2-(2H-Benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl) phenol.

C₂₀H₂₅N₃  323.43

USP Bisoctrizole Resolution Mixture RS

A mixture of approximately 1.5% of bisoctrizole isomer [phenol, 2,2′-methylenebis[6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)]] in a matrix of bisoctrizole.