Bisoctrizole
(bis ok' tri zole).
Click to View Image
C41H50N6O2 658.90
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] [103597-45-1].
» Bisoctrizole contains not less than 96.0 percent and not more than 102.0 percent of C41H50N6O2, calculated on the as-is basis.
Packaging and storage— Preserve in well-closed containers, and store at controlled room temperature.
USP Reference standards 11
USP Bisoctrizole RS Click to View Structure
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.
Identification—
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Limit of bisoctrizole related compound A and the bisoctrizole isomer—
Diluent, Solution A, Solution B, and Mobile phase— Proceed as directed in the Assay.
Standard stock solution A— Dissolve an accurately weighed quantity of USP Bisoctrizole RS in tetrahydrofuran to obtain a solution having a known concentration of about 0.65 mg per mL.
Standard stock solution B— Dissolve an accurately weighed quantity of USP Bisoctrizole Related Compound A RS in tetrahydrofuran to obtain a solution having a known concentration of about 0.40 mg per mL.
Standard solution— Quantitatively 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.
Test solution— Proceed as directed for the Assay preparation.
Chromatographic system— Proceed as directed in the Assay. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the resolution, R, between bisoctrizole and the bisoctrizole isomer is not less than 1.5. [note—For identification purposes, the relative retention times are about 0.42 for bisoctrizole related compound A and about 1.1 for the bisoctrizole isomer. ]
Procedure— Inject a volume (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of bisoctrizole related compound A taken by the formula:
10,000(C /W)(rU / rS)
in which C is the concentration, in mg per mL, of USP Bisoctrizole Related Compound A RS; W is the weight, in mg, of Bisoctrizole taken; rU is the peak response for bisoctrizole related compound A in the Test solution; and rS is the peak response for bisoctrizole related compound A in the Standard solution: not more than 0.5% of bisoctrizole related compound A is found. Calculate the percentage of the bisoctrizole isomer taken by the formula:
10,000(C/W)(rU / rS)
in which C is the concentration, in mg per mL, of USP Bisoctrizole RS; W is the weight, in mg, of Bisoctrizole taken; rU is the peak response for the bisoctrizole isomer in the Test solution; and rS is the peak response for bisoctrizole in the Standard solution: not more than 4.0% of the bisoctrizole isomer is found.
Related compounds—
Diluent, Solution A, Solution B, Mobile phase, and Chromatographic system— Proceed as directed in the Assay.
Test solution— Proceed as directed for the Assay preparation.
Procedure— Inject a volume (about 10 µL) of the Test solution into the chromatograph, record the chromatogram, and measure all the peak responses. Calculate the percentage of each impurity in the portion of Bisoctrizole taken by the formula:
100(ri / rs)
in which ri is the peak response for each individual impurity, and rs is the sum of the responses of all the peaks: not more than 0.1% of any individual impurity, excluding bisoctrizole related compound A and the bisoctrizole isomer, is found. Not more than 4.0% of total impurities, including bisoctrizole related compound A, and the bisoctrizole isomer, determined in the test for Limit of bisoctrizole related compound A and the bisoctrizole isomer, is found.
Assay—
Diluent— Prepare a mixture containing tetrahydrofuran and a 0.2% (w/v) aqueous solution of 1-pentane sulfonic acid sodium salt (60:40).
Solution A— Prepare a filtered and degassed solution containing 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— Prepare a filtered and degassed solution containing 0.4 g of 1-pentane sulfonic acid sodium salt, 1000 mL of methanol, and 0.5 mL of phosphoric acid.
Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— Dissolve an accurately weighed quantity of USP Bisoctrizole Resolution Mixture RS in tetrahydrofuran, and dilute quantitatively with Diluent to obtain a solution having a known concentration of about 0.8 mg per mL of bisoctrizole.
Standard preparation— Transfer about 80 mg of USP Bisoctrizole RS, accurately weighed, to a 100-mL volumetric flask. Dissolve in 60 mL of tetrahydrofuran, dilute with Diluent to volume, and mix.
Assay preparation— Transfer about 80 mg of Bisoctrizole, accurately weighed, to a 100-mL volumetric flask. Dissolve in 60 mL of tetrahydrofuran, dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 346-nm detector and a 3.0-mm × 25-cm column that contains packing L1. The flow rate is about 0.8 mL per minute. The column temperature is maintained at 40. The chromatograph is programmed as follows.
Time
(minutes)
Solution A
(%)
Solution B
(%)
Elution
0–1 70 30 isocratic
1–11 70®3 30®97 linear gradient
11–27 3 97 isocratic
27–28 3®70 97®30 linear gradient
Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for bisoctrizole and 1.1 for the bisoctrizole isomer; the resolution, R, between bisoctrizole and the bisoctrizole isomer is not less than 1.5; and the relative standard deviation for replicate injections of the Standard preparation is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C41H50N6O2 in the portion of Bisoctrizole taken by the formula:
100C(rU / rS)
in which C is the concentration, in mg per mL, of USP Bisoctrizole RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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Topic/Question Contact Expert Committee
Monograph Feiwen Mao, M.S.
Senior Scientific Liaison
1-301-816-8320
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