Authorized USP Pending Standards

Version 1 Bicalutamide / 1

A: Infrared Absorption h197Mi.

BRIEFING
B: The retention time of the major peak in the

Bicalutamide, page 738 of PF 31(3) [May–June 2005]. This chromatogram of the Assay preparation corresponds to that
monograph was published in PF for public review and comment
before the establishment of the USP Pending Standards web page. in the chromatogram of the Standard preparation, as obtained
The MD-OOD Expert Committee reviewed the comment and has
approved the monograph as an Authorized USP Pending Standard. in the Assay.
The following is a summary of the comment received and the Expert
Committee’s decision: Water, Method I h921i: not more than 0.5%.
 Comment Summary: A comment was received from the
innovator suggesting changes to the procedures and specifica- Residue on ignition h281i: not more than 0.1%.
tions. Response: Because the USP Bicalutamide monograph
based on the innovator’s submission was published on page 876
of PF 33(5) [Sept.–Oct. 2007], the comment is not incorporated Heavy metals, Method II h231i: 0.002%.

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in this Pending Standard.
Limit of alcohol—
(MD-OOD: F. Mao) RTS—58864
Standard solution—Prepare a solution of alcohol in
dimethyl sulfoxide having a known concentration of about

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an en IZ
0.1 mg of alcohol per mL.
Add the following: Test solution—Dissolve an accurately weighed portion of
&Bicalutamide Bicalutamide in dimethyl sulfoxide to obtain a solution
St P R
having a concentration of about 100 mg per mL.
v.1 Authorized June 11, 2007
Chromatographic system (see Chromatography h621i)—
O
The gas chromatograph is equipped with a headspace injector,
a flame-ionization detector, and a 0.53-mm 6 30-m capillary
SP H

column, the internal wall of which is coated with a 1.0-mm

film of liquid phase G43. The carrier gas is helium, flowing at
U T

a rate of about 4.4 mL per minute with a split ratio of 1 : 5.

C18H14F4N2O4S 430.37 The chromatograph is programmed as follows. Initially the
AU

temperature of the column is maintained at 708 for 2 minutes,

Propanamide, N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-
then increased at a rate of 208 per minute to 1708, and
fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-, (+)-.
maintained at 1708 for 1 minute. The injector port
(+)-4’-Cyano-a,a,a-trifluoro-3-[(p-fluorophenyl)sulfonyl]-2- temperature is maintained at 1408; the headspace sampler
methyl-m-lactotoluidide [90357-06-5]. temperature is maintained at 808; and the detector temperature
is maintained at 2508. Chromatograph the Standard solution,
and record the peak responses as directed for Procedure: the
» Bicalutamide contains not less than 98.0 percent
retention time for alcohol is about 1.6 minutes; the column
and not more than 102.0 percent of
effiiciency is not less than 10,000 theoretical plates; and the
C18H14F4N2O4S, calculated on the anhydrous basis.
relative standard deviation for three injections of the Standard

Packaging and storage—Preserve in tight containers, and solution is not more than 5.0%.

store at room temperature. Procedure—Transfer 1.0 mL each of the Test solution and

USP Reference standards h11i—USP Bicalutamide RS. the Standard solution to separate 20-mL headspace vials.

USP Bicalutamide Related Compound A RS. Record the chromatograms, and measure the peak area for the
alcohol peak. Calculate the amount of alcohol in ppm in the
Identification—
portion of Bicalutamide taken by the formula:

This monograph has been developed under USP’s Pending Standards Guideline, and is not a USP–NF monograph.
http://www.usp.org
# 2007 The United States Pharmacopeial Convention All Rights Reserved.
 Authorized USP Pending Standards
2 / Bicalutamide Version 1

Time Solution A Solution B

106(CS / CU)(rU / rS)
(minutes) (%) (%) Elution

in which CS is the concentration, in mg per mL, of alcohol in 0–16.5 67 33 isocratic

the Standard solution; CU is the concentration, in mg per mL, 16.5–26.5 67?40 33?60 linear gradient

of Bicalutamide in the Test solution; and rU and rS are the 26.5–32.5 40?5 60?95 linear gradient

alcohol peak areas in the chromatograms obtained from the 32.5–32.6 5?67 95?33 linear gradient

Test solution and the Standard solution, respectively: not 32.6–35.0 67 33 isocratic

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more than 500 ppm of alcohol (C2H5OH) is found. Chromatograph the System suitability solution, and record the
Chromatographic purity— peak responses as directed for Procedure: the relative
Solution A, Solution B, and Diluent—Prepare as directed in retention times are about 0.62 for bicalutamide related

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the Assay. compound A isomer A, 0.65 for bicalutamide related

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Mobile phase—Use variable mixtures of Solution A and
Solution B as directed for Chromatographic system. Make
compound A isomer B, and 1.0 for bicalutamide; and the
resolution, R, between bicalutamide related compound A
St P R
adjustments if necessary (see System Suitability under isomer A and bicalutamide related compound A isomer B is
Chromatography h621i). not less than 0.8, and the resolution, R, between bicalutamide
O
System suitability solution—Dissolve accurately weighed related compound A isomer B and bicalutamide is not less
quantities of USP Bicalutamide Related Compound A RS and than 8.5.
USP Bicalutamide RS in Diluent to obtain a solution having Procedure—Separately inject equal volumes (about 10 mL)
SP H

known concentrations of about 0.005 mg per mL and 0.05 mg of the Standard solution and Test solution into the
per mL, respectively. chromatograph, record the chromatograms, and measure all
U T

Standard solution—Dissolve an accurately weighed quan- of the peak responses. Calculate the percentage of each
AU

tity of USP Bicalutamide RS in Diluent to obtain a solution impurity in the portion of Bicalutamide taken by the formula:
having a known concentration of about 1 mg per mL.
Test solution—Transfer about 25 mg of Bicalutamide, 2.5(CW)(ri / rS)

accurately weighed, to a 25-mL volumetric flask, dissolve in

in which C is the concentration, in mg per mL, of USP
and dilute with Diluent to volume, and mix.
Bicalutamide RS in the Standard solution; W is the weight, in
Chromatographic system (see Chromatography h621i)—
mg, of Bicalutamide in the Test solution; ri is the peak
The liquid chromatograph is equipped with 270-nm detector
response for each impurity obtained from the Test solution;
and a 4.0-mm 6 10-cm column that contains 3-mm packing
and rS is the bicalutamide peak response obtained from the
L1. The flow rate is about 1 mL per minute. The
Standard solution. Disregard any peak less than 0.02%: not
chromatograph is programmed as follows.
more than 0.10% of any individual impurity is found; and not
more than 0.50% of total impurities is found.

This monograph has been developed under USP’s Pending Standards Guideline, and is not a USP–NF monograph.
http://www.usp.org
# 2007 The United States Pharmacopeial Convention All Rights Reserved.
Authorized USP Pending Standards
Version 1 Bicalutamide / 3

Assay— Chromatographic system (see Chromatography h621i)—

Solution A—Prepare a filtered and degassed 0.01% (v/v) The liquid chromatograph is equipped with a 270-nm detector
solution of trifluoroacetic acid in water. and a 4.0-mm 6 10-cm column that contains 3-mm packing
Solution B—Prepare a filtered and degassed 0.01% (v/v) L1. The flow rate is about 1.0 mL per minute. Chromatograph

solution of trifluoroacetic acid in acetontrile. the System suitability solution and the Standard preparation,
Diluent—Prepare a mixture of Solution A and Solution B and record the peak responses as directed for Procedure: the
(1 : 2). resolution, R, between bicalutamide related compound A

Mobile phase—Prepare a filtered and degassed mixture of isomer B and bicalutamide is not less than 2.0; and the

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Solution A and Solution B (52 : 48). Make adjustments if relative standard deviation for replicate injections of the
necessary (see System Suitability under Chromatography Standard preparation is not more than 2.0%.

h621i). Procedure—Separately inject equal volumes (about 10 mL)

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System suitability solution—Prepare a solution of USP of the Standard preparation and the Assay preparation into

an en IZ
Bicalutamide RS and USP Bicalutamide Related Compound
A RS in Diluent to obtain a solution having known
the chromatograph, record the chromatograms, and measure
the responses for the major peaks. Calculate the quantity, in
St P R
concentrations of about 0.05 mg per mL and 0.005 mg per mg, of C18H14F4N2O4S in the portion of Bicalutamide taken by
mL, respectively. the formula:
O
Standard preparation—Dissolve an accurately weighed
quantity of USP Bicalutamide RS in Diluent to obtain 500C(rU / rS)
SP H

a solution having a known concentration of about 50 mg per

in which C is the concentration, in mg per mL, of USP
mL.
Bicalutamide RS in the Standard preparation; and rU and rS
U T

Assay preparation—Transfer about 25 mg of Bicalutamide,

are the peak responses obtained from the Assay preparation
accurately weighed, to a 25-mL volumetric flask, dissolve in
and the Standard preparation, respectively.&
AU

and dilute with Diluent to volume, and mix. Pipet 1.0 mL of

this solution into a 20-mL volumetric flask, dilute with
Diluent to volume, and mix.

This monograph has been developed under USP’s Pending Standards Guideline, and is not a USP–NF monograph.
http://www.usp.org
# 2007 The United States Pharmacopeial Convention All Rights Reserved.