usP 33

ENTIFICATION IP on-The Sample is pre~ared as follows.] [N ,nple: Transfer a po~Ion of the melted Suppositories ob­S~ined in the Assay, equ1valent to 1 g of aspirin, to a 125-ml

nicai flask. Add 20 ml of_ alco~ol, and warm until com­cfetely disinteg~ted. Cool 1n an ice bat~ for 5 min, filter, and ~vaparate the f1ltrat~ to dryness: the res1due meets the require­rnents of the follow1ng tests.

• A. Heat the residue wi~h wate_r for several min, cool, and add 1 or 2 drops of teme chlonde TS: a violet-red color is produced.

• 8. INFIARED ABSORPTION (197K)

ASSAY • paOCEDURE

(NOTE-ln this Assay, use chloroform that recently was satu­rated with water.]

Chromatographic column: Uniformly pack a chromato­graphic tube, as described in the test for Procedure: Limit of Free Salicylic Acid, with a mixture of 3 g of chromatographic siliceous earth and 2 ml of sodium bicarbonate solution (1 in 12) prepared on the day of use.

Standard stock solution: Transfer 50 mg of USP Aspirin RS to a 50-ml volumetric flask, add 0.5 ml of glacial acetic acid, and add chloroform to volume.

Standard solution: O.OS mg/ml USP Aspirin RS from Stan­dard stock solution diluted with a solution of glacial acetic acid in chloroform (1 in 100)

sample solution: Tare a small dish and glass rod, place in the dish NLT 5 Suppositories, heat gently on a steam bath until melted, then stir, and cool while stirring. Transfer a portion of the mass, equivalent to 50 mg of aspirin, to a 50-ml volumetric flask containing 1 ml of a solution of hydro­chloric acid in methanol (1 in 50), add 40 ml of chloro­form, and add chloroform to volume.

Spectrometric conditions (See Spectrophotometry and Light-Scattering (851 ).) Mode: UV Analytical wavelength: 280 nm Cell: 1 cm Blank: Chloroform

Analysis: Pipet 5 ml of the Sample solut!on i~to the column, wash with 5 ml of chloroform, then aga1n w1th 25 ml of chloroform, and discard the washings. Without delay, elute into a 100-ml volumetric flask with 1 O ml of a solution of glacial acetic acid in chloroform (1 in 1 O), and then with 85 ml of a solution of glacial acetic acid in chloroform (1 In 100), and dilute with the latter solvent to volume. Without delay, determine the absorbances of the eluted Sample solu­tion and Standard solution. Calculate the percentage of (9HsO◄ in the portion of Sup­positories taken:

Result = (Au/As) x (Cs/Cu) X 100

~ = absorbance of the Sample solution As = absorbance of the Standard solution Cs = concentration of USP Aspirin RS in the Standard

solution (µg/ml) . . . Cu = nominal concentration of aspmn 1n the Sample

solution (µg/mL) Acceptance criteria: 90.0<¾r 1 l 0.0%

IMPURITIES Organk lmpurftles ' PllocEDURE: LIMIT OF FREE SALICYLIC ACID

Ferric chloride-urea reagent: To a mixture of 8 ml of ferric chloride solution (6 in 10) and 42 ml of 0.05 N hy­drochloric acid, add 60 g of urea. Dissolve t~e urea by ~irling and without the aid of heat,. ~nd ad1ust the result­mg solution, if necessary, by the add1t1on of 6 N hydrochlo­ric acid to a pH of 3.2. [NOTE-Prepare on the day of use.]

Chromatographic column: lnsert a small pledget of glass wool above the stem constriction of a 20- x 2.5-cm chro­matographic tube, and uniformly pack with a mixture of 1

Official Monographs / Aspirin 2043

. . . h and Q.5 ml of 5 M g of chromatograph1c s1hceous ea;. layer pack a similar phosphoric acid. Directly above ht. '

5silicedus earth, and 2

mixture of 3 g of chromatograp ,e ml of Fe"ic chloride~rea rea9enr suitable quantity of

Standard stock solutron: Dissobve_ ª a solution containing salicylic acid in chloroforrn to O tain 150 µg/ml of salicylic acid. f h Standard stock so/u-

Standard solution: Pipet 5 rnl O t e . . 10 rnl of tion into a 50-rnl volurnetric fla~k co~tami~gl O rnl of a methanol, 0.1 ml of hydr~h!orrc ac, ' ª!1

10 Add chlo-solution of glacial acetic ac1d m ether (1 in ). roform to volume. d I d lace in

Sample solution: Tare a small dish an 9 ass ro , P the dish NLT 5 Suppositories, heat ~ently ?n a steam rb!th

until melted, then stir, and cool wh1le st1rnng. T~a.nsfe ee portion of the mass equivalent to 50 mg of asp1nn (s Sample solution in the Assay) to a small beaker. Add 1 O ml

' · ·1 ct· 1 ed With of chloroform, warm slightly, and stIr untI isso v · the aid of 5 ml of chloroform, transfer to the chromat?· graphic adsorption column. Pass 50 m~ of chlor?form m several portions through the column, nnse the_ t1p of the chromatographic tube with chloroform, and d1scard the el­uate. lf the purple zone reaches the botto~ of the tube, discard the column, and repeat the test w1th a smaller quantity of melted Suppositories. . Elute the adsorbed salicylic acid into a 100-ml volumetnc flask containing 20 ml of methanol an~ 0.2 ml of h~dro­chloric acid by passing two 10-ml portIons of a _solut1on of glacial acetic acid in water-saturated ether (1 1n 1 O), and then 30 ml of chloroform, through the column, and dilute the eluate with chloroform to volume.

Spectrometric conditions (See Spectrophotometry and Light-Scattering (851 ).) Mode: UV Analytical wavelength: 306 nm Cell: 1 cm Blank: A solvent mixture of the sarne composition as the Standard solution

Analysis Samples: Standard so/ution and Sample so/ution Concomitantly determine the absorbances.

Acceptance criteria: The absorbance of the Sample solu­tion is NMT 3.0% that of the Standard solution.

ADDITIONAL REQUIREMENTS • PACKAGING AND STORAGE: Preserve in well-closed containers,

in a cool place. • USP REFERENCE STANDARDS (11)

USP Aspirin RS

Asplrln Tablets

DEFINITION Aspirin Tablets contain NLT 90.0% and NMT 110.0% of the

labeled amount of aspirin (C9HsO◄). Tablets of larger than 81-mg size contain no sweeteners or other flavors. [NOTE-Tab­lets that are enteric-coated meet the requirements for Aspirin Delayed-Release Tablets.]

IDENTIFICATION • A. PRocEDURE

Sample: 1 Tablet Analysis: Crush and boil Sample with 50 ml of water for 5 min, cool, and add 1 or 2 drops of ferric chloride TS.

Acceptance criteria: A violet-red colar is produced. • B. INFRARED ABSORPTION (197K)

Sample: Shake a quantity of finely powdered Tablets, equivalent to 500 mg of aspirin, with 1 O ml of alcohol for several min. Centrifuge_ the mixture. Pour off the clear super­natant, and evaporate It to dryness. Dry the residue in a vacuum at 60° for 1 h.

2044 Aspirin / Officia/ Monographs

ASSAY • PROCEDURE

Mobile phase: Dissolv 2 f d' in a mixture of 8S0 Le f 9 ° so ium 1-heptanesulfonate and adjust with glac~I O t"'."ate~dand 150 ml of acetonitrile, Diluent· A . . ace ,e ac, to a pH of 3.4.

St d . cetonitnle and formic acid (99·1) an ard solutlon· o 5 / · Sample stock solut· : ~g ~L of USP ~spirin RS in Diluent aspirin from finei ion. rans er an equ,valent to 100 mg of

contai~er. Add 2J cfº1dered_ Tablets (NLT 20), to a suitable orously for 10 . · md O Di(uent and 1 O beads. Shake vig-Sam 1 • mm, an centnfuge. tiori ;it~oiut1~n: Dilute .ª volume of the S~mple stock so/u-orr vo umes of Diluent. [NOTE-Relam the remaining PS

1. 'º,~ of Samp/e stock solution for the test for Limit of Free a 1cy IC Acid.]

Chromatographic system (See Chromatography (621 ), System Suitability) M~~ K · Detector: UV 280 nm Column: 4.0-mm x 30-cm; packing L 1 Flow rate: 2 ml/min lnjection size: 1 O µL

System suitablllty Sample: Standard solution Suitability requirements

Talling factor: NMT 2.0 Relative standard deviation: NMT 2.0%

Analysis Samples: Standard solution and Sample solution Calculate the percentage of ( 9HaO4 in the portion of Tab­lets taken:

Result = (ru/rs) x (Cs/Cu) x 100

ru = peak response of the aspirin from the Sample solution

rs = peak response of the aspirin from the Standard solution

Cs = concentration of USP Aspirin RS in the Standard solution (mg/ml)

Cu = nominal concentration of the Sample solution (mg/ml)

Acceptance criteria: 90.0%-110.0%

PERFORMANCE TESTS • DISSOLUTION (711)

O.OS M acetate buffer: Mix 2.99 g of sodium acetate trihy­drate and 1.66 ml of glacial acetic acid with water to obtain 1000 ml of solution having a pH of 4.50 ± O.OS.

Medium: 0.05 M acetate buffer; 500 ml Apparatus 1 : 50 rpm Time: 30 min Standard solution: USP Aspirin RS of a known concentra­tion in Medium [NOTE- Prepare the Standard solution at the time of use. An amount of alcohol not to exceed 1 % of the total volume of the Standard solution may be used to bring the Reference Standard into solution before dilution with Medium.] . • h sample solution: Sample per Dissolution (711 ). D1lute w1t Medium, if necessary, and f1lter.

Analysis . Samples: Standard solution and Sa~ple solut,on Determine the amount of ( 9HaO4 d1s~olved f~om ~V ab­sorbances at the wavelength of the 1sosbest1c pomt of as­pirin and salicylic acid at 265 ± 2 nm of th~ Sample solu­tion in comparison with the Standard solut,on.

Tolerances: NLT 80% (Q) of the labeled amount of ( 9Hs0 4 is dissolved.

• UNIFORMITY OF DOSAGE UNJTS (905): Meet the requirements

IMPURITIES Organlc lmpurltles • PROCEDURE! LIMIT OF fRH SAUCYLIC ACID . . Mobile phase and Diluent: Prepare as directed ,n the

Assay.

Usp 33

Standard solution: 0.015 mg/!'f1L of s~licylic acid in the Standard solution prepared as directed m the _Assay.

Sample solutlon: Use the Sample stock solut,on from the Assay. d d' Chromatographlc system: Procee as irected in lhe Assay.

System sultablllty . Sample: Standard solut,o~ . . . [Non-The relative retentIon times for_sahcyhc acid and aspirin are about 0.7 and 1.0, respect1vely.]

Sultablllty requirements . . . Resolutlon: NLT 2.0, between sallcyhc :c1d and aspirin Relatlve standard deviatlon: NMT 4.0 ¾> for the salj. cylic acid peak responses

Analysls Samples: Standard solution and Sa,:nple soluti~n Calculate the percentage of C1H6O3 m the portIon of Tab. lets taken:

Result = (ru/rs) x (Cs/Cu) x 100

ru = peak response of the salicylic acid from the Sample solution

rs = peak response of the salicylic acid from the Standard solution

Cs = concentration of USP Salicylic Acid RS in the Standard solution (mg/ml)

Cu = concentration of aspirin in the Sample solution as determined in the Assay (mg/ml)

Acceptance criterla: NMT 0.3%. For Tablets that are coated, NMT 3.0%.

ADDITIONAL REQUIREMENTS • PACKAGING AND STORAGE! Preserve in tight containers. Pre­

serve flavored or sweetened Tablets of 81-mg size or smaller in containers holding NMT 36 Tablets each.

• USP REFERENCE STANDARDS (11) USP Aspirin RS USP Salicylic Acid RS

Buffered Asplrln Tablets DEFINITION Buffered Aspirin Tablets contain Aspirin and suitable buffering

agents. Tablets contain NLT 90.0% and NMT 11 O.O% oi the labeled amount of aspirin (C9H8O4).

IDENTIFICATION • A. PROCEDURE

Sample: 1 Tablet An~lysis: Crush and boil Sample with 50 ml of water for 5 mm, coo!, and add 1 or 2 drops of ferric chloride TS.

Acceptance criterla: A violet-red color is produced. • B. INFRARED ABSORPTION (197K)

Sam1;>le: Shake a quantity of finely powdered Tablets, equ1valent to_ 500 mg of aspirin, with 1 o ml of Chloroforrn for severa! mm. Centrifuge the mixture. Pour off the clear supernatant, and evaporate it to dryness. Dry the residue in a vacuum at 60° for 1 h.

ASSAY • PROCEDURE

~obile _phase: Dissolve 2 g of sodium 1-heptanesulfonate m ª m,~ture ?f 850 ml of water and 150 ml of acetonitrile, ªnd adiust w,th glacial acetic acid to a pH of 3.4.

Dlluent: Acet?nitrile and formic acid (99: 1) Standard solut1on: 0.5 mg/ml of USP Aspirin RS in Oiluent Samp)e stock solution: Transfer an equivalent to 100 rng 01 aspin~, from finely powdered Tablets (NLT 20), to a suita~le contamer. Add 2~.0 ml of Di/uent and 10 beads. Shake vig· orously for 1 O mm, and centrifuge.