Pentazocine and Aspirin Tablets, chemical structure, molecular formula, Reference Standards

Pentazocine and Aspirin Tablets

(Monograph under this new title—to become official February 1,2005)

(Current monograph title is Pentazocine Hydrochloride and Aspirin Tablets)

»Pentazocine and Aspirin Tablets contain an amount of Pentazocine Hydrochloride equivalent to not less than 90.0percent and not more than 110.0percent of the labeled amount of pentazocine (C19H27NO)and not less than 90.0percent and not more than 110.0percent of the labeled amount of aspirin (C9H8O4).

Packaging and storage— Preserve in tight,light-resistant containers.

USP Reference standards á11ñ— USP Aspirin RS.USP Pentazocine RS.USP Salicylic Acid RS.

Thin-layer chromatographic identification test á201ñ—

Test solution— Shake a quantity of finely powdered Tablets,equivalent to about 25mg of pentazocine and 650mg of aspirin,with 10mLof a mixture of chloroform and methanol (1:1)in an ultrasonic bath for 2minutes.Allow the solids to settle.

Standard solutions— Prepare a solution of USP Pentazocine RSin a mixture of chloroform and methanol (1:1)containing 2.5mg per mL.Using the same solvent,prepare a solution of USP Aspirin RScontaining 65mg per mL.

Developing solvent system: ethyl acetate,methanol,and formic acid (90:5:5).

Procedure— Evaporate the solvents from the spots in warm circulating air.Place the plate in the developing chamber,and after developing the plate,remove it,and mark the solvent front.Evaporate the solvents thoroughly in warm circulating air,and examine the plate under short-wavelength UVlight.Expose the plate to iodine vapor for about 5minutes,and observe.Then spray the plate with an iodoplatinate spray reagent prepared by dissolving 300mg of platinic chloride in 100mLof water and adding 100mLof potassium iodide solution (6in 100):the chromatogram obtained with the Test solutionshows two principal spots which correspond in RFvalues,size,and intensity of color with the spots obtained with the Standard solutions.

Nonaspirin salicylates—

Ferric chloride–urea reagent— To a mixture of 8mLof ferric chloride solution (6in 10)and 42mLof 0.05Nhydrochloric acid add 60g of urea.Dissolve the urea by swirling and without the aid of heat,and adjust the resulting solution,if necessary,with 6Nhydrochloric acid to a pHof 3.2.Prepare on the day of use.

Procedure— Insert a small pledget of glass wool above the stem constriction of a 20-×2.5-cm chromatographic tube,and uniformly pack with a mixture of about 1g of chromatographic siliceous earth and 0.5mLof 5Mphosphoric acid.Directly above this layer,pack a similar mixture of about 3g of chromatographic siliceous earth and 2mLof Ferric chloride–urea reagent.To an accurately weighed quantity of finely powdered Tablets,equivalent to 50mg of aspirin,add 10mLof chloroform,stir for 3minutes,and transfer to the chromatographic adsorption column with the aid of 5mLof chloroform.Pass 50mLof chloroform in several portions through the column,rinse the tip of the chromatographic tube with chloroform,and discard the eluate.If the purple zone reaches the bottom of the tube,discard the column,and repeat the test with a smaller quantity of powdered Tablets.

Elute the adsorbed salicylic acid into a 100-mLvolumetric flask containing 20mLof methanol and 4drops of hydrochloric acid by passing two 10-mLportions of a 1in 10solution of glacial acetic acid in water-saturated ether,and then 30mLof chloroform,through the column,and dilute the eluate with chloroform to volume.Dissolve a suitable,accurately weighed quantity of salicylic acid in chloroform to obtain a Standard solution containing 150µg of salicylic acid per mL.Pipet 5mLof this solution into a 50-mLvolumetric flask containing 10mLof methanol,2drops of hydrochloric acid,and 10mLof a 1in 10solution of glacial acetic acid in ether.Add chloroform to volume,and mix.Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 306nm,using as the blank a solvent mixture of the same composition as that of the Standard solution:the absorbance of the solution from the Tablets does not exceed that of the Standard solution,any necessary adjustment being made for having used a smaller sample (3.0%).

Dissolution á711ñ—

Medium: water;900mL.

Apparatus 1: 80rpm.

Time: 30minutes.

Strongly basic, anion-exchange resin—Mix a suitable quantity of anion-exchange resin with 10volumes of dilute glacial acetic acid (1in 50)and shake for 20minutes.Allow the resin to settle,and decant the supernatant.Repeat the acetic acid washing four more times.Wash with water until 5.0mLof the water wash gives a negligible response when substituted for 5.0mLof the Test solution,and carried through the Determination of dissolved pentazocinebelow.

Test solution— To a suitable 50-mLflask,add 0.4g of Strongly basic anion-exchange resin,and 25mLof the solution under test.Shake by mechanical means for 15minutes.Allow to settle,and use the clear supernatant in the following determinations.

Determination of dissolved pentazocine—

STANDARD SOLUTION— Prepare a solution in dilute glacial acetic acid (1in 50)containing 13µg of USP Pentazocine RSper mL.

PROCEDURE— Transfer 5.0mLportions of the Test solution,the Standard solution,and water to serve as the reagent blank,into three separate 125-mLseparators.To each separator add 10mLof a filtered 1in 4000solution of bromocresol purple in dilute glacial acetic acid (1in 50)and 20.0mLof chloroform.Insert the stopper,and shake gently for 1minute,accurately timed.Allow the layers to separate,and determine the absorbances of the clear chloroform layers from the Standard solutionand the Test solutionin 1-cm cells at the wavelength of maximum absorbance at about 408nm with a suitable spectrophotometer against the chloroform layer from the reagent blank.Determine the amount of pentazocine (C19H27NO)in the Test solutionby comparison with the Standard solution.

Determination of dissolved aspirin—

STANDARD SOLUTION— Prepare a solution containing 15µg of USP Salicylic Acid RSper mLof 0.1Nsodium hydroxide.

PROCEDURE— Transfer 1.0mLof the Test solutionto a 25-mLvolumetric flask containing 1.0mLof sodium hydroxide solution (1in 10),and swirl.Allow to stand for 10minutes.Dilute with water to volume,and mix.Concomitantly determine the absorbances of the Test solutionand of the Standard solution in 1-cm cells at the wavelength of maximum absorbance at about 296nm with a suitable spectrophotometer,using 0.1Nsodium hydroxide as the blank.Calculate the quantity,in mg,of aspirin (C9H8O4)in the Test solutionby comparison with the Standard solution,using the quantity (180.16/138.12),the ratio of the molecular weight of aspirin to that of salicylic acid,to convert the amount of salicylic acid measured to the amount of aspirin in the Test soluiton.

Tolerances— Not less than 80%(Q)of the labeled amount of C19H27NOand not less than 70%(Q)of the labeled amount of C9H8O4are dissolved in 30minutes.

Uniformity of dosage units á905ñ: meet the requirements.

Assay—

Chromatographic column— Use a 200-mm tube consisting of about a 90-mm length of 22-mm tubing fused to about a 100-mm length of 5-mm tubing having a stopcock at the bottom of this section.Place a pledget of glass wool at the bottom of the 5-mm portion just above the stopcock.Transfer a suitable quantity of sulfonic acid cation-exchange resin to a beaker and wash three times with water,discarding the water wash each time by decantation.Cover the resin with a mixture of methanol and 6Nhydrochloric acid (1:1),and allow to stand for 1hour.Decant the acid wash;if it is colored yellow or orange,repeat this step until the wash is almost colorless.Then wash the resin by repeated 15-minute soakings in a mixture of methanol and water (1:1)followed by decantation until the wash is neutral to wide-range indicator paper.Fill the tube to a height of 100mm with slurry of the washed resin in a mixture of methanol and water (1:1).Wash the column with 25mLof methanol and water (1:1).

Test solutions— Weigh and finely powder not fewer than 20Tablets.Transfer a portion of the freshly powdered Tablets,equivalent to about 25mg of pentazocine and 650mg of aspirin,accurately weighed,to a suitable 250-mLflask.Add 100.0mLof a mixture of methanol and water (1:1),and shake by mechanical means for 20minutes.Centrifuge a suitable quantity for 5minutes.Transfer 25.0mLof the clear supernatant to the prepared Chromatographic column,followed by five 10-mLportions of the mixture of methanol and water (1:1),collecting the eluate in a 250-mLvolumetric flask containing 10.0mLof 2.5Nsodium hydroxide.Dilute with water to volume,and mix.Reserve this asTest solution 1for the Determination of aspirin.Next pass through the column five 5-mLportions of a mixture of methanol and 6Nhydrochloric acid (1:1)followed by 10mLof water.Collect the eluate in a 100-mLvolumetric flask,dilute with water to volume,and use this asTest solution 2for the Determination of pentazocine.

Determination of aspirin—

STANDARD SOLUTION— Prepare a solution of USP Salicylic Acid RSin 0.1Nsodium hydroxide having a known concentration of about 18µg per mL.

PROCEDURE— Pipet 4mLof Test solution 1into a 100-mLvolumetric flask,dilute with 0.1Nsodium hydroxide to volume,and mix (Diluted test solution).Concomitantly determine the absorbances of the Diluted test solution and the Standard solutionin 1-cm cells at the wavelength of maximum absorbance at about 296nm with a suitable spectrophotometer,using 0.1Nsodium hydroxide as the blank.Calculate the quantity,in mg,of aspirin (C9H8O4),in the portion of Tablets taken by the formula:

25C(180.16/138.12)(AU/AS),

in which Cis the concentration,in µg per mL,of USP Salicylic Acid RSin the Standard solution;(180.16/138.12)is the ratio of the molecular weight of aspirin to that of salicylic acid;and AUand ASare the absorbances of Diluted test solution and the Standard solution,respectively.

Determination of pentazocine—

STANDARD SOLUTION— Prepare a solution of USP Pentazocine RSin a mixture of water,methanol,and 6Nhydrochloric acid (6:1:1)having a known concentration of about 62.5µg per mL.

PROCEDURE— Concomitantly determine the absorbances of Test solution 2and the Standard solution,in 1-cm cells at the wavelength of maximum absorbance at about 278nm,with a suitable spectrophotometer,using the solvent for the Standard solutionas the blank.Calculate the quantity,in mg,of pentazocine (C19H27NO)in the portion of Tablets taken by the formula:

0.4C(AU/AS),

in which Cis the concentration,in µg per mL,of USP Pentazocine RSin the Standard solution;and AUand ASare the absorbances of Test solution 2and the Standard solution,respectively.

(Official February 1,2005)

Auxiliary Information— Staff Liaison:Daniel K.Bempong,Ph.D.,Scientist

Expert Committee:(PA2)Pharmaceutical Analysis 2

USP28–NF23Page 1502

Pharmacopeial Forum:Volume No.28(6)Page 1847

Phone Number:1-301-816-8143