NOV 0 8 2006
`
`THE UNITED STATES PHARMACOPEIA
`
`THE NATIONAL FORMULARY
`
`By authority of The United States Pharmacopeial
`Convention, meeting at Washington, D.C., March 9-13,
`2005. Prepared by the Council of Experts and published
`by the Board of Trustees
`
`Official from May I, 2007
`
`The designation on the cover of this publication, "USP NF
`2007," is for ease of identification only. The publication
`contains two separate compendia: The United States
`Pharmacopeia, Thirtieth Revision, and the National
`Formulary, Twenty-Fifth Edition.
`
`KNOBBE, MArlTENS, OLSON & BEAR, LLP
`2u4'.) MAIN ST.
`14rn FLOOR
`IRVl~'.E. CA 92614
`
`THE UNITED STATES PHARMACOPEIAL CONVENTION
`12601 Twinbrook Parkway, Rockville, MD 20852
`
`r I
`
`I
`
`,
`
`11
`
`2007
`
`USP 30
`
`NF 25
`
`I
`
`I Volume 2
`
`I
`
`'
`
`- -
`
`".l
`
`Page 1
`
`LUPIN EX. 1034
`Lupin v. iCeutica
`US Patent No. 9,017,721
`
`

`
`11::
`i'!j
`I:
`I'
`:I
`i
`
`USR'30
`
`Add the following:
`•Diclofenac Potassium
`
`c H Cl2KN02
`334.24
`B~~;neacetic acid, 2-[(2,6-dichlorophenyl)amino ]-, monopotas(cid:173)
`shun salt.
`Potassium [o-(2,6-dichloroanilino )phenyl] acetate
`
`[15307-81-0 ].
`
`» Diclofenac Potassium contains not less than 99.0
`percent and not more than 101. 0 percent of
`C14H10C!z:KN02, calculated on the dried basis.
`Packaging and storage-Preserve in light-resistant containers, and
`store at controlled room temperature.
`USP Reference standards ( 11 )-USP Diclofenac Potassium RS.
`,USP Diclofenac Related Compound A RS.
`Identification-
`A:
`Infrared Absorption (197K).
`B: Ultraviolet Absorption (197U)(cid:173)
`Solution: 0.1 mg per mL.
`Medium: methanol.
`C:
`It meets the requirements of the flame test for Potassium
`(191).
`pH (791): between 7.0 and 8.5, in a 1% aqueous solution.
`Loss on drying (731)-Dry it at 105° under vacuum for 3 hours: it
`loses not more than 0.5% of its weight.
`Heavy metals, Method II (231): not more than 10 ppm.
`Related compounds-
`pH 2.5 Phosphate buffer-Mix equal volumes of 0.01 M
`phosphoric acid and 0.01 M monobasic sodium phosphate. If
`necessary, adjust with additional portions of the appropriate
`components to a pH of 2.5 ± 0.2.
`Mobile phase-Prepare a filtered and degassed mixture of
`methanol and pH 2.5 Phosphate buffer (70: 30). Make adjustments
`if necessary (see System Suitability under Chromatography (621)).
`Diluent-Prepare a mixture of methanol and water (70 : 30).
`Standard solution-Prepare a solution of USP Diclofenac Related
`Compound A RS in methanol having a known concentration of
`about 0.25 mg per mL. Quantitatively dilute an accurately measured
`volume of this stock solution with Diluent to obtain a solution
`having a known concentration of about 1.5 µL per mL.
`Resolution solution-Prepare a solution in Diluent containing 40
`µg per mL of diethyl phthalate, 0.5 mg per mL of USP Diclofenac
`Potassium RS, and 22.5 µg per mL of USP Diclofenac Related
`Compound A RS.
`Test solution-Transfer about 50 mg of Diclofenac Potassium,
`a~curately weighed, to a 100-mL volumetric flask, dissolve in and
`dilute with Diluent to volume, and mix.
`. c_hromatographic system (see Chromatography (621))-The
`hqu1d chromatograph is equipped with a 254-nm detector and a
`4.6-mm x 25-cm column that contains packing L7. The flow rate is
`about 1.0 mL per minute. Chromatograph the Resolution solution,
`and record the peak responses as directed for Procedure: the relative
`retention times are about 0.5 for diethyl phthalate, 0.7 for diclofenac
`related compound A, and 1.0 for diclofenac potassium; and the
`resolution, R, between diethyl phthalate and diclofenac related
`compound A is not less than 4.0. Chromatograph the Standard
`solution, and record the peak responses as directed for Procedure:
`the relative standard deviation for replicate injections is not more
`than 5.0%.
`
`Official Monographs I Diclofenac
`
`1921
`
`Procedure-Separately inject equal volumes (about 30 µL) of the
`Standard solution and the Test solution into the chromatograph,
`record the chromatograms, and measure the peak responses.
`Calculate the percentage of diclofenac related compound A in the
`portion of Diclofenac Potassium taken by the formula:
`
`lO(C/W)(rul rs)
`
`in which C is the concentration, in µg per mL, of USP Diclofenac
`Related Compound A RS in the Standard solution; Wis the quantity,
`in mg, of Diclofenac Potassium taken to prepare the Test solution;
`and ru and rs are the diclofenac related compound A peak responses
`obtained from the Test solution and the Standard solution,
`respectively: not more than 0.1 % of diclofenac related compound
`A is found. Calculate the percentage of each other impurity in the
`portion of Diclofenac Potassium taken by the formula:
`
`10( C/W)(r;I rs)
`in which r; is the individual peak response of each impurity obtained
`from the Test solution; and the other terms are as defined above: not
`more than 0.1 % of each individual impurity is found, and not more
`than 0.3% of total impurities is found.
`Assay-Dissolve about 300 mg ofDiclofenac Potassium, accurately
`weighed, in 50 mL of glacial acetic acid, and titrate with 0.1 N
`perchloric acid VS, determining the endpoint potentiometrically.
`Perform a blank determination, and make any necessary correction
`(see Titrimetry (541)). Each mL of 0.1 N perchloric acid is
`equivalent to 33.424 mg of C14H10CbKN02 ..... usP3o
`
`Add the following:
`,.. Diclofenac Potassium Tablets
`
`» Diclofenac Potassium Tablets contain not less than
`90.0 percent and not more than 110.0 percent of the
`labeled amount of diclofenac potassium
`(C14H10ChKN02).
`
`Packaging and storage-Preserve in tight, light-resistant contain(cid:173)
`ers, and store at controlled room temperature.
`USP Reference standards (11)-USP Diclofenac Potassium RS.
`USP Diclofenac Related Compound A RS.
`Identification-
`A: The retention time of the diclofenac peak in the chromato(cid:173)
`gram of the Assay preparation corresponds to that of the Standard
`preparation, as obtained in the Assay.
`B:
`It meets the requirements of the flame test for Potassium
`(191) .
`Dissolution (711)-
`simulated intestinal fluid (without enzyme); 900 mL.
`Medium:
`Apparatus 2: 50 rpm.
`Time: 60 minutes.
`Procedure-Determine the amount of C14H10Cl2KN02 dissolved
`by employing UV absorption at the wavel(1ngth of maximum
`absorbance at about 276 nm on portions of the solution under test
`passed through a 0.45-µm filter, suitably diluted with Medium, if
`necessary, in comparison with a Standard solution having a known
`
`Page 2
`
`

`
`1922
`
`Diclofenac I Official Monographs
`
`USP 30
`
`concentration of USP Diclofenac Potassium RS in the same Medium.
`C_alculate the percentage of diclofenac potassium (C14H 10Cl2KN02)
`dissolved by the formula:
`
`A x C x 900 x 100
`u
`s
`
`in which Au and As are the absorbances obtained from the solution
`under tes~ an~ the Standard solution, respectively; Cs is the
`concentrat10n, m mg per mL, of the Standard solutioll" 900 is the
`volume, in mL, of Medium; 100 is the conversio~ factor to
`perce°:tage; and LC is the Tablet label claim, in mg, of diclofenac
`potassmm.
`Tolerances-Not less than 80% (Q) of the labeled amount of
`C14H 10Cl2KN02 is dissolved in 60 minutes.
`Uniformity of dosage units: meets the requirements.
`Loss on drying (731 )-Dry it at 105° ± 2° for 3 hours : it loses not
`more than 5.0% of its weight.
`Limit of potassium-
`Standard-Accurately transfer about 50.00 mg of potassium
`chloride into a fused quartz crucible.
`Sample-Transfer n?t few~ than five diclofenac potassium 50-mg
`Tablets, accurately weighed, mto a fused quartz crucible.
`Blank-Prepare a dilution of 10% cesium chloride (1 in 50).
`Test solut!ons-Place crucibles conta~ing the Standard, Sample,
`for 8 hours to ash the
`and Blank m a muffle furnace at 550
`contained material. Pipet 1.0 mL of concentrated hydrochloric acid
`and 1.0 mL of concentrated nitric acid into each cooled crucible.
`Heat each crucible on a hot plate to dissolve the residue. Transfer
`quantitatively, without filtering, the contents of each crucible to 100-
`mL volumetric fl.ask~, and d~lute with water to volume. Pipet 1.0 mL
`from each volumetric fl.ask mto separate 100-mL volumetric fl.asks
`pipet 2.0 mL of 10% cesium chloride solution into each fl.ask and
`dilute with water to volume.
`'
`Procedure-Concomitantly determine the absorbances of the Test
`solutions and Blank at the potassium emission line at 766.5 nm with
`a suitable atomic absorption spectrophotometer (see Spectropho(cid:173)
`tometry and Light-Scattering (851)) equipped with an air-acetylene
`flame. Plot the absorbances of the Test solutions versus their
`potassium content. Calculate the weight percentage of potassium in
`each Tablet: not less than 2.40% and not more than 2.94% is found;
`and not less than 90.0% and not more than 110.0% of the calculated
`theoretical amount of potassium is found.
`Related compounds-
`pH 2.5 Phosphate buffer, Mobile phase, Diluent, Resolution
`solution, and Chromatographic system-Prepare as directed in the
`Assay.
`Stan_dard solution-Dissolve an accurately weighed quantity of
`USP Diclofenac Related Compound A RS in Diluent, and dilute
`quantitatively, and stepwise if necessary, to obtain a solution having
`a known concentration of about 50 µg per mL.
`Test solution-Use the Assay preparation, prepared as directed in
`the Assay.
`Procedure-Separately inject equal volumes (about 30 µL) of the
`Standard solution, and the Test solution into the chromatograph,
`record the chromatograms, and measure the peak responses.
`Calculate the percentage of diclofenac related compound A in the
`portion of Tablets taken by the formula:
`
`lO(CIA)(rul rs)
`
`in which C is the concentration, in µg per mL, of diclofenac related
`c?mpound A in the Standard solution; A is the quantity, in mg, of
`diclofenac pota~sium in the J?Orti~n of Tablets taken to prepare the
`A~say preparation, as determmed m the Assay; and ru and rs are the
`diclofena~ related compound A peak responses obtained from the
`Tes~ solutzo_n and the Standard solution, respectively: not more than
`0.1 Yo of diclofenac related compound A is found. Calculate the
`
`percentage_ of each of the other impurities, other than diethyl
`phthalate, if present, in the portion of Tablets taken by the formula:
`
`lO(C/A)(r;/ rs)
`
`in which r, is the response of an individual impurity peak obtained
`from the Test solution, and the other terms are as defined above: not
`more than 0.1 % of each individual impurity is found, and not more
`than 0.3% of total impurities is found.
`Assay-
`pH ~.5 P~osphate buffer-Mix equal volumes of 0.01 M
`phosphonc a~id an~ 0.01 J\:f. monobasi.c sodium phosphate. If
`necessary, adjust with addit10nal port10ns of the appropriate
`components to a pH of 2.5 ± 0.2.
`Mobile phase-Prepare a filtered and degassed mixture of
`~ethanol and pH 2.5 Phosphate buffer (70: 30). Make adjustments
`ifne~essary (see System_ Suitability under Chromatography (621)).
`Diluent-Prepare a mixture of methanol and water (70 : 30).
`Standar4 preparation-J?issolve an accurately weighed quantity
`~f USP Diclofe~ac _Potassmm RS in Diluent, and dilute quantita(cid:173)
`tively, and stepwise if necessary, to obtain a solution having a known
`concentration of about 50 µg per mL.
`Assay preparation-Weigh and finely powder not fewer than 20
`Tab~ets. Transfer an accurately weighed portion of the powder
`eqmvalent to about 50 mg of diclofenac potassium, to a 100-mL
`v?lumetJ;ic fl.ask. Add about 70 mL of Diluent, stir for 60 minutes,
`dilute witli Diluent to volume, mix, and centrifuge.
`Resolution so!ution-Prepare a solution in Diluent containing 40
`µg per. mL of diethyl phthalate, 0.5 mg per mL of USP Diclofenac
`Potassium RS, and 37.5 µg per mL of USP Diclofenac Potassium
`Related Compound A RS.
`. C~romatographic s:ystem. (see Chromatography (621))-The
`hqmd chromatograph is eqmpped with a 254-nm detector and a
`4.6-mm x 25-cm colmnn that contains 5-µm packing L7. The flow
`rate is about 1 mL per minute. Chromatograph the Resolution
`solution, and record the peak responses as directed for Procedure:
`the resolution, R, between diethyl phthalate and diclofenac related
`compound A is not less than 2.5, and the resolution R between
`diclofenac related compound A and diclofenac is not les~ than 3.5.
`Chromatograp~ the Standard preparation, and record the peak
`responses as directed for Procedure: the relative standard deviation
`for replicate injections is not more than 2.0%.
`Procedure-Separately inject equal volumes (about 10 µL) of the
`Standard preparation and the Assay preparation into the chromat(cid:173)
`ograph,. record the chromatograms, and measure the responses for
`the ma1or peaks. Calculate the quantity, in mg, of diclofenac
`potassium (C14H10Cl2KN02) in each Tablet taken by the formula:
`(VC/20)(rul rs)
`in which V is the volume of the fl.ask used to prepare the Assay
`p~eparation; C is the concentration, in mg per mL, of l]SP
`Diclofenac Potassium RS in the Standard preparation; and ru andls
`are the peak responses obtained from the Assay preparation and the
`Standard preparation, respectively.,..usPJo
`
`Diclofenac Sodium
`
`0
`
`&:£~'
`
`diUJl1
`C14H10Cl2NNa02 318.13
`Benzeneacetic acid, 2-[(2,6-dichlorophenyl)arnino ]-, monoso
`salt.
`Sodium [o-(2,6-dichloroanilino )phenyl]acetate
`
`[ J 5307-79-6J·
`
`1,
`
`!
`
`I!
`
`Page 3
`
`

`
`fenac Sodium contains not less than 99.0 percent
`.
`1
`» ~icot more than 101.0 percent of C14H10Cl2NNa02,
`nlaoted on the dried basis.
`an
`1
`ca cu
`mng and storage-Preserve in tight, light-resistant contain(cid:173)
`packa.,--
`ers.p Reference standards ( 11 )-USP Diclofenac Sodium RS. USP
`V~ l J, iiac Related Compound A RS.
`Die o1e
`tification-
`Jde~ Infrared Absorption (197K):
`.
`~- The retention time of the diclofenac peak m the chromato-
`.. of the Test solution corresponds to that of the Resolution
`grfition as obtained in J?e test for ~hror:iatographic purity.
`.
`so C: The residue obtamed by 1gmtmg 1t responds to the flame test
`for Sodium (191).
`Color of solution-A 1 in 20 solution of it in methanol is colorless
`to faintly yellow, and the absorbance of the solution, determined in a
`1-cm cell at 440 nm, is not more than 0.050, methanol being used as
`the blank.
`·
`Clarity of solution-The solution prepared as directed under Color
`a/solution is not significantly less clear than an equal volume of
`methanol contained in a similar vessel and examined similarly.
`pij: (791): between 7.0 and 8.5, in a solution (1 in 100).
`Loss on drying (731)-Dry it at 105° to 110° for 3 hours: it loses
`not more than 0.5% of its weight.
`Heavy metals, Method II (231 )-To prepare the Test Preparation,
`use a 100-mL borosilicate glass beaker or a quartz crucible. If the
`residue is not completely white after the ignition at 500° to 600°, add
`enough hydrogen peroxide to dissolve it, heat gently until dry, and
`ignite for 1 hour. Repeat the hydrogen peroxide treatment and
`ignition until the residue is completely white. Proceed as directed in
`Test Preparation, beginning with "Cool, add 4 mL of 6 N
`hydrochloric acid." The limit is 0.001 %.
`Chromatographic purity-
`pH 2.5 Phosphate buffer-Mix equal volumes of 0.01 M
`phosphoric acid and 0.01 M monobasic sodium phosphate. If
`necessary, adjust with additional portions of the appropriate
`component to a pH of 2.5 ± 0.2.
`Mobile phase-Prepare a filtered and degassed mixture of
`methanol and pH 2.5 Phosphate buffer (700: 300). Make adjust(cid:173)
`ments if necessary (see System Suitability under Chromatography
`(621)). [NOTE-Increasing the proportion of buffer increases
`resolution.]
`Diluent-Prepare a mixture of methanol and water (70 : 30).
`Standard solution-Prepare a solution of USP Diclofenac Related
`Compound A RS in methanol having a known concentration of
`about 0.75 mg per mL. Quantitatively dilute an accurately measured
`volume of this stock solution with Diluent to obtain a solution
`having a known concentration of about 1.5 µg per mL.
`Resolution solution-Prepare a solution in Diluent containing 20
`µg of diethyl phthalate, 7.5 µg of USP Diclofenac Related
`Compound A RS, and 0.75 mg of USP Diclofenac Sodium RS per
`mL.
`Test solution-Transfer about 75 mg of Diclofenac Sodium,
`a~curately weighed, to a 100-mL volumetric flask, dissolve in and
`dilute with Diluent to volume, and mix.
`. C,hromatographic system (see Chromatography (621))-The
`hqmd chromatograph is equipped with a 254-nm detector and a
`4.6-mm x 25-cm column containing packing L7 (end-capped). The
`flow rate is about 1 mL per minute. Chromatograph the Resolution
`solution, and record the peak responses as directed for Procedure:
`t~e relative retention times are about 0.5 for diethyl phthalate, 0.6 for
`diclofenac related compound A, and 1.0 for diclofenac; and the
`resolution, R, between diethyl phthalate and diclofenac related
`compound A is not less than 2.2, and that between diclofenac related
`compound A and diclofenac is not less than 6.5. Chromatograph the
`Standard solution, and record the peak responses as directed for
`Procedure: the relative standard deviation for replicate injections is
`not more than 5%.
`Procedure-Separately inject equal volumes (about 10 µL) of the
`Standard solution and the Test solution into the chromatograph,
`record the chromatograms, and measure the peak responses over a
`
`Official Monographs I Diclofenac
`
`1923
`
`period of 2.5 times the retention time of diclofenac. Calculate the
`percentage of diclofenac related compound A in the portion of
`Diclofenac Sodium taken by the formula:
`
`lO(C I Jf')(rul rs)
`
`in which C is the concentration, in µg per mL, of USP Diclofenac
`Related Compound A RS in the Standard solution; Wis the quantity,
`in mg, of Diclofenac Sodium taken to prepare the Test solution; and
`ru and rs are the diclofenac related compound A peak responses
`obtained from the Test solution and the Standard solution,
`respectively: not more than 0.2% is found. Calculate the percentage
`of each other impurity in the portion of Diclofenac Sodium taken by
`the formula:
`
`10( CI Jf')(r,I rs)
`
`in which r, is the response of an individual impurity peak obtained
`from the Test solution, and the other terms are as defined above: not
`more than 0.2% of any individual impurity is found. The sum of all
`of the impurities found is not more than 0.5%.
`Assay-Dissolve about 450 mg of Diclofenac Sodium, accurately
`weighed, in 25 mL of glacial acetic acid, and titrate with 0.1 N
`perchloric acid VS, determining the endpoint potentiometrically.
`Perform a blank determination, and make any necessary correction.
`Each mL of O.lN perchloric acid is equivalent to 31.81 mg of
`C,4H10Cl2NNa02.
`
`Diclofenac Sodium Delayed-Release
`Tablets
`
`» Diclofenac Sodium Delayed-Release Tablets contain
`not less than 90.0 percent and not more than 110.0
`percent of the labeled amount of diclofenac sodium
`(C14H10Cl2NNa02).
`
`Packaging and storage--Preserve in tight, light-resistant contain(cid:173)
`ers.
`USP Reference standards (11)-USP Diclofenac Sodium RS. USP
`Diclofenac Related Compound A RS.
`Identification-
`A: The retention time of the diclofenac peak in the chromato(cid:173)
`gram of the Assay preparation corresponds to that in the
`chromatogram of the Standard preparation, as obtained in the Assay.
`B:
`It meets the requirements of the flame test for Sodium ( 191).
`Dissolution (711 )-Proceed as directed for Procedure for Method B
`under Apparatus I and Apparatus 2, Delayed-Release Dosage
`Forms.
`ACID STAGE-
`Medium: 0.1 N hydrochloric acid; 900 mL.
`Apparatus 2 (paddles constructed of, or coated with, polytef being
`used): 50 rpm .
`Procedure-At the end of 2 hours, remove each Tablet, or the
`major portion thereof if the Tablet is not intact, from the individual
`vessels, and subject them to the test in the Buffer stage. To the 0.1 N
`hydrochloric acid remaining in each vessel, add 20.0 mL of 5 N
`sodium hydroxide, and stir for 5 minutes. Determine the amount of
`C14H 10Cl,NNa02 dissolved from UV absorbances at the wavelength
`of maximum absorbance at about 276 nm on filtered portions of the
`solution under test in comparison with a Standard solution prepared
`as follows. Transfer about 68 mg of USP Diclofenac Sodium RS,
`accurately weighed, to a 100-mL volumetric flask, add 10.0 mL of
`0.1 N sodium hydroxide, dilute with water to volume, and mix.
`Transfer 2.0 mL of this solution to a second 100-mL volumetric
`flask, dilute with a mixture of 0.1 N hydrochloric acid and 5 N
`sodium hydroxide (900 : 20) to volume, and mix. This Standard
`solution contains about 13.6 µg of USP Diclofenac Sodium RS per
`mL.
`
`Page 4
`
`

`
`1924
`
`Dicloxacillin I Official Monographs
`
`USP 30
`
`I I
`I 1
`
`BUFFER STAGE-
`pH 6.8 Phosphate buffer-Dissolve 76 g of tribasic sodium
`phosphate in water to obtain 1000 mL of solution. Mix 250 mL of
`this solution with 750 mL of 0.1 N hydrochloric acid, and, if
`necessary, adjust with 2 N hydrochloric acid or 2 N sodium
`hydroxide to a pH of 6.8 ± 0.05.
`Medium: pH 6.8 Phosphate buffer; 900 mL.
`Apparatus 2: 50 rpm.
`Procedure-At the end of 45 minutes, determine the amount of
`C14H10Cl2NNa02 dissolved from UV absorbances at the wavelength
`of maximum absorbance at about 276 nm on filtered portions of the
`solutions under test, suitably diluted with Medium, in comparison
`with a Standard solution prepared as follows. Transfer about 68 mg
`of USP Diclofenac Sodium RS, accurately weighed, to a 100-mL
`volumetric flask, add 10.0 mL of 0.1 N sodium hydroxide, dilute
`with water to volume, and mix. Transfer 2.0 mL of this solution to a
`second 100-mL volumetric flask, dilute with Medium, as obtained in
`the Buffer stage, to volume, and mix. This Standard solution
`contains about 0.02 mg of USP Diclofenac Sodium RS per mL.
`Tolerances-Not less than 75% (Q) of the labeled amount of
`C14H10Cl2NNa02 is dissolved.
`Uniformity of dosage units (905): meet the requirements.
`Chromatographic purity-
`pH 2.5 Phosphate buffer, Mobile phase, Diluent, Resolution
`solution, and Chromatographic system-Proceed as directed in the
`Assay.
`Standard solution-Prepare a solution having a known concen(cid:173)
`tration of about 0.8 mg per mL of USP Diclofenac Related
`Compound A RS in methanol. Dilute an accurately measured
`volume of this stock solution with Diluent to obtain a solution
`having a known concentration of about 4 µg per mL.
`Test solution-Use the Assay preparation, prepared as directed in
`the Assay.
`Procedure-Separately inject equal volumes (about 10 µL) of the
`Standard solution and the Test solution into the chromatograph,
`record the chromatograms, and measure the peak responses over a
`period of 40 minutes. Calculate the percentage of diclofenac related
`compound A in relation to the quantity of diclofenac sodium in the
`Tablets taken by the formula:
`
`lO(C!A)(rul rs)
`in which C is the concentration, in µg per mL, of USP Diclofenac
`Related Compound A RS in the Standard solution; A is the quantity,
`in mg, of diclofenac sodium (C14H10Cl2NNa02) in the Tablets taken
`for the Assay, as determined in the Assay; and ru and rs are the
`diclofenac related compound A peak responses obtained from the
`Test solution and the Standard solution, respectively: not more than
`0. 5% is found. Calculate the percentage of each other impurity, other
`than diethyl phthalate, if present, in relation to the diclofenac sodium
`in the Tablets taken by the formula:
`
`10( CIA)(r;I rs)
`in which r, is the peak response for each impurity obtained from the
`Test solution, and the other terms are as defined above: not more than
`1.0% of any individual impurity is found, and not more than 1.5% of
`total impurities is found.
`Assay-
`pH 2.5 Phosphate buffer-Mix equal volumes of 0.01 M
`phosphoric acid and 0.01 M monobasic sodium phosphate. If
`necessary, adjust with additional portions of the appropriate
`component to a pH of 2.5 ± 0.2.
`Mobile phase-Prepare a filtered and degassed mixture of
`methanol and pH 2.5 Phosphate buffer (700: 300). Make adjust(cid:173)
`ments if necessary (see System Suitability under Chromatography
`(621)). [NOTE-Increasing the proportion of buffer increases
`resolution.]
`Diluent-Prepare a mixture of methanol and water (70 : 30).
`Standard preparation-Prepare a solution of USP Diclofenac
`Sodium RS in Diluent having a known concentration of about 0.75
`mg per mL.
`Resolution solution-Prepare a solution in Diluent containing 20
`µg of diethyl phthalate, 7.5 µg of USP Diclofenac Related
`Compound A RS, and 0.75 mg of USP Diclofenac Sodium RS per
`mL.
`
`Assay preparation-Transfer 20 Tablets to a volumetric flask of
`such capacity that when filled to volume, a concentration of about
`0.75 mg of diclofenac sodium per mL is obtained. Add Diluent to
`about 70% of the capacity of the flask, and shake by mechanical
`means for not less than 30 minutes to disintegrate the Tablets. Cool
`to room temperature, dilute with Diluent to volume, and mix. Pass a
`portion of the solution through a filter having a 0.5-µm or finer
`porosity, and use the filtrate as the Assay preparation.
`Chromatographic system (see Chromatography ( 621) )-The
`liquid chromatograph is equipped with a 254-nm detector and a
`4.6-mm x 25-cm column that contains packing L7 (end-capped).
`The flow rate is about 1 mL per minute. Chromatograph the
`Resolution solution, and record the peak responses as directed for
`Procedure: the relative retention times are about 0.5 for diethyl
`phthalate, 0.6 for diclofenac related compound A, and 1.0 for
`diclofenac; and the resolution, R, between diethyl phthalate and
`diclofenac related compound A is not less than 2.2, and between
`diclofenac related compound A and diclofenac is not less than 6.5.
`Chromatograph the Standard preparation, and record the peak
`responses as directed for Procedure: the relative standard deviation
`for replicate injections is not more than 2.0%.
`Procedure-Separately inject equal volumes (about 10 µL) of the
`Standard preparation and the Assay preparation into the chromat(cid:173)
`ograph, record the chromatograms, and measure the peak responses.
`Calculate the quantity, in mg, of diclofenac sodium
`(C14H 10Cl2NNa02) in each Tablet taken by the formula:
`(VC/20)(rulrs)
`
`in which C is the concentration, in mg per mL, of USP Diclofenac
`Sodium RS in the Standard preparation; Vis the volume of the flask
`used, in mL; and ru and rs are the diclofenac peak responses obtained
`from the Assay preparation and the Standard preparation,
`respectively.
`
`Dicloxacillin Sodium
`
`Cl
`
`0
`Nao-{/
`O~
`\,,H
`"f+~;CHs
`!'.
`~--
`CH~
`S
`
`• H20
`
`H H
`
`CH3
`
`C19H16Cl2N3Na05S · H10 510.32
`4-Thi~-1-azabicyclo[3 .2.0]hept~e-2-carboxylic acid, ?-[[[3-(2~:
`dichlorophenyl)-5-methyl-4-isoxazolyl]carbonyl]ammo ]-3 ,3-·s
`methyl-7-oxo-, monosodium salt, monohydrate, [2 -
`{21X,51X,6,8)]-.
`.
`Monosodium (2S,5R, 6R)-6-[3-(2,6-dichlorophenyl)-5-methyI-t:so(cid:173)
`xazo lecarboxamido ]-3 ,3-dimethyl-7-oxo-4-thia-1-aza 1?](cid:173)
`clo[3.2.0]heptane-2-carboxylate monohydrate
`[13412-64-
`Anhydrous 492.32
`[343-55-5].
`
`·
`
`» Dicloxacillin Sodium contains the equivalent of not
`less than 850 µg of dicloxacillin (C 19H17ClzN30sS) per
`mg.
`
`. m RS.
`Packaging and storage---Preserve in tight conta~n~rs.
`USP Reference standards ( 11 )-USP Dicloxacillm Sodzu
`.
`Identification-
`.
`Infrared Absorption ( 197K).
`A:
`Ignite about 100 mg: a 1 in 20 solution of the
`B:
`acetic acid responds to the tests for Sodium (191).
`Crystallinity ( 695): meets the requirements.
`. .
`pH (791): between 4.5 and 7.5, in a solution contaJ11J11g
`mL.
`
`10 !Ilg per
`
`residue in
`
`Page 5