Printed on: Mon Nov 07 2022, 10:40:10 PM(EST) Status: Currently Official on 08-Nov-2022 DocId: GUID-049C8CB0-4B74-4DBC-80A2-C501A9F04F95_2_en-US

Printed by: Stuart Walters Official Date: Official as of 01-May-2020 Document Type: USP @2022 USPC
Do Not Distribute DOI Ref: djt3y DOI: https://doi.org/10.31003/USPNF_M18685_02_01
1

Standards labels to calculate the concentrations as

Clopidogrel Tablets appropriate.]
Phosphate buffer and Mobile phase—Prepare as directed in
» Clopidogrel Tablets contain Clopidogrel Bisulfate the Assay under Clopidogrel Bisulfate.
System suitability solution—Dissolve accurately weighed
equivalent to not less than 90.0 percent and not quantities of USP Clopidogrel Bisulfate RS and USP Clopidogrel
more than 110.0 percent of the labeled amount of Related Compound B RS in methanol, and dilute with
clopidogrel (C16H16ClNO2S). methanol to obtain a solution having concentrations of about
100 µg per mL and 200 µg per mL, respectively. Transfer 5 mL
Packaging and storage—Preserve in well-closed of this solution to a 200-mL volumetric flask, dilute with
containers, and store at controlled room temperature. Mobile phase to volume, and mix.
USP Reference standards á11ñ— Standard solution—Dissolve accurately weighed quantities
USP Clopidogrel Bisulfate RS of USP Clopidogrel Bisulfate RS, USP Clopidogrel Related
USP Clopidogrel Related Compound A RS Compound A RS, and USP Clopidogrel Related
(+)-(S)-(o-Chlorophenyl)-6,7-dihydrothieno[3,2-c] Compound C RS in methanol to obtain a solution having
pyridine-5(4H)-acetic acid. known concentrations of about 40 µg per mL, 250 µg per mL,
USP Clopidogrel Related Compound B RS and 300 µg per mL, respectively. Transfer 5 mL of this solution
Methyl (±)-(o-chlorophenyl)-4,5-dihydrothieno[2,3-c] to a 200-mL volumetric flask, and dilute with Mobile phase to
pyridine-6(7H)-acetate, hydrochloride. volume. This solution contains about 1 µg of clopidogrel
USP Clopidogrel Related Compound C RS bisulfate per mL, 6 µg of clopidogrel related compound A per
Methyl (−)-(R)-(o-chlorophenyl)-6,7-dihydrothieno[3,2- mL, and 7.5 µg of clopidogrel related compound C per mL.
c]pyridine-5(4H)-acetate, hydrogen sulfate. Test solution—Weigh and finely powder not fewer than 20
Tablets. Transfer an accurately weighed portion of the

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Identification— powder, equivalent to about 75 mg of clopidogrel (free base),
Change to read: to a 200-mL volumetric flask, add 5 mL of methanol, dilute
with Mobile phase to volume, and mix. Allow to stand for 10
A: ▲Spectroscopic Identification Tests á197ñ, minutes, and mix. Pass a portion of this solution through a
Ultraviolet-Visible Spectroscopy: 197U▲ (CN 1-May-2020)— filter having a 0.45-µm or finer porosity, and use the filtrate
Spectral range: 250 to 300 nm.
Solution—Use the test solution prepared as directed in the
test for Uniformity of dosage units.
ci after discarding the first 5 mL.
Chromatographic system (see Chromatography á621ñ)—The
liquid chromatograph is equipped with a 220-nm detector
B: The retention time of the major peak in the and 4.6-mm × 15-cm column that contains packing L57. The
chromatogram of the Assay preparation corresponds to that in flow rate is about 1.0 mL per minute. Chromatograph the
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the chromatogram of the Standard preparation, as obtained in System suitability solution, and record the peak responses as
the Assay. directed for Procedure: the relative retention times are about
0.8 and 1.2 for the two enantiomers of clopidogrel related
Dissolution á711ñ— compound B and 1.0 for clopidogrel; and the resolution, R,
Medium: pH 2.0 hydrochloric acid buffer (see Buffer between clopidogrel and the first enantiomer of clopidogrel
Solutions under Reagents, Indicators, and Solutions); 1000 mL. related compound B is greater than 2.5. Chromatograph the
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Apparatus 2: 50 rpm. Standard solution, and record the peak responses as directed
Time: 30 minutes. for Procedure: the relative retention times are about 0.5 for
Standard solution—Dissolve an accurately weighed quantity clopidogrel related compound A, 1.0 for clopidogrel and
of USP Clopidogrel Bisulfate RS in 20.0 mL of methanol, and 2.0 for clopidogrel related compound C; and the relative
dilute quantitatively, and stepwise if necessary, with Medium standard deviation for replicate injections is not more than
to obtain a solution having a known concentration 15% for each peak.
corresponding to that of the solution under test. Procedure—Inject equal volumes (about 10 µL) of the
Procedure—Determine the amount of C16H16ClNO2S Standard solution and Test solution into the chromatograph,
dissolved by employing UV absorption at a wavelength of record the chromatograms, and measure the peak responses.
about 240 nm on filtered portions of the solution under test Calculate the percentage of clopidogrel related compounds A
in comparison with the Standard solution. and C in the portion of Tablets taken by the formula:
Tolerances—Not less than 80% (Q) of the labeled amount
of C16H16ClNO2S is dissolved in 30 minutes. 20(321.82/419.90)(C/W)(rU/rS)
Uniformity of dosage units á905ñ: meet the requirements.
Procedure for content uniformity—Using a suitable in which 321.82 is the molecular weight of clopidogrel;
volumetric flask, place 1 Tablet in 50.0 mL of 0.1 N 419.90 is the molecular weight of clopidogrel bisulfate; C is
hydrochloric acid. Sonicate for 5 minutes, and cool. the concentration, in µg per mL, of the relevant clopidogrel
Quantitatively transfer 5.0 mL of this solution to the flask, and related compound in the Standard solution; W is the weight,
dilute with 0.1 N hydrochloric acid to 50.0 mL. Pass a portion in mg, of clopidogrel in the portion of Tablets used to
of the solution through a suitable filter having a 0.45-µm or prepare the Test solution based on the labeled quantity of
finer porosity, discarding the first 5 mL of the filtrate. clopidogrel per Tablet, Tablet weight, and the weight of the
Determine the amount of clopidogrel by employing UV portion of Tablets used; and rU and rS are the peak responses
absorption at the wavelength of maximum absorbance at of the corresponding related compounds obtained from the
about 270 nm, in comparison with a Standard solution Test solution and the Standard solution, respectively.
having a known concentration of USP Clopidogrel Bisulfate RS Calculate the percentage of any other impurity (excluding
in 0.1 N hydrochloric acid. clopidogrel related compound B) in the portion of Tablets
Related compounds— [NOTE—For all clopidogrel related taken by the formula:
compounds, the concentrations are expressed as bisulfate
salts. Use bisulfate salt equivalents stated on USP Reference 20(321.82/419.90)(CC/W)(rU/rS)

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Printed on: Mon Nov 07 2022, 10:40:10 PM(EST) Status: Currently Official on 08-Nov-2022 DocId: GUID-049C8CB0-4B74-4DBC-80A2-C501A9F04F95_2_en-US
Printed by: Stuart Walters Official Date: Official as of 01-May-2020 Document Type: USP @2022 USPC
Do Not Distribute DOI Ref: djt3y DOI: https://doi.org/10.31003/USPNF_M18685_02_01
2

in which CC is the concentration of clopidogrel bisulfate, in µg obtain a solution having a known concentration of about
per mL, in the Standard solution; rU is the peak response of any 0.1 mg of clopidogrel bisulfate per mL.
other impurity obtained from the Test solution; rS is the peak Assay preparation—Weigh and finely powder not fewer
response of clopidogrel peak obtained from the Standard than 20 Tablets. Transfer an accurately weighed portion of the
solution; and the other terms are as defined above: not more powder, equivalent to about 75 mg of clopidogrel (base), to a
than 1.2% of clopidogrel related compound A is found, not 100-mL volumetric flask, and add 50 mL of methanol. Sonicate
more than 1.5% of clopidogrel related compound C is found, for 5 minutes, and stir for 30 minutes. Dilute with methanol
not more than 0.2% of any other single impurity (excluding to volume, and mix. Transfer 5.0 mL of this solution to the
clopidogrel related compound B) is found, and not more than flask, dilute with methanol to 50.0 mL, and mix. Pass a portion
2.5% of total impurities (excluding clopidogrel related of this solution through a filter having a 0.45-µm or finer
compound B) is found. porosity, and use the filtrate after discarding the first 5 mL.
Assay— [NOTE—For all clopidogrel related compounds, the Procedure—Separately inject equal volumes (about 10 µL)
concentrations are expressed as bisulfate salts. Use bisulfate of the Standard preparation and the Assay preparation into the
salt equivalents stated on USP Reference Standards labels to chromatograph, record the chromatograms, and measure the
calculate the concentrations as appropriate.] responses for the analyte peaks. Calculate the quantity, in mg,
Phosphate buffer, Mobile phase, and Chromatographic of clopidogrel (C16H16ClNO2S) in the portion of Tablets taken
system—Proceed as directed in the Assay under Clopidogrel by the formula:
Bisulfate.
System suitability preparation—Dissolve accurately weighed 1000(321.82/419.90)C(rU/rS)
quantities of USP Clopidogrel Bisulfate RS and USP Clopidogrel
Related Compound B RS in methanol, and quantitatively dilute in which 321.82 is the molecular weight of clopidogrel;
with methanol to obtain a solution having concentrations of 419.90 is the molecular weight of clopidogrel bisulfate; C is
the concentration, in mg per mL, of USP Clopidogrel

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about 100 µg per mL and 200 µg per mL, respectively. Transfer
5 mL of this solution to a 200-mL volumetric flask, dilute with Bisulfate RS in the Standard preparation; and rU and rS are the
Mobile phase to volume, and mix. peak responses obtained from the Assay preparation and the
Standard preparation—Dissolve an accurately weighed Standard preparation, respectively.
quantity of USP Clopidogrel Bisulfate RS in methanol to ci
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