Packaging and storage—
Preserve in tight, light-resistant containers.
Thin-layer chromatographic identification test 
201
—
Test solution—
Shake a quantity of finely powdered Tablets, equivalent to about 25 mg of pentazocine and 650 mg of aspirin, with 10 mL of a mixture of chloroform and methanol (1:1) in an ultrasonic bath for 2 minutes. Allow the solids to settle.
Standard solutions—
Prepare a solution of
USP Pentazocine RS in a mixture of chloroform and methanol (1:1) containing 2.5 mg per mL. Using the same solvent, prepare a solution of
USP Aspirin RS containing 65 mg 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 UV light. Expose the plate to iodine vapor for about 5 minutes, and observe. Then spray the plate with an iodoplatinate spray reagent prepared by dissolving 300 mg of platinic chloride in 100 mL of water and adding 100 mL of potassium iodide solution (6 in 100): the chromatogram obtained with the Test solution shows two principal spots which correspond in RF values, size, and intensity of color with the spots obtained with the Standard solutions.
Nonaspirin salicylates—
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 the urea by swirling and without the aid of heat, and adjust the resulting solution, if necessary, with 6 N hydrochloric acid to a pH of 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 1 g of chromatographic siliceous earth and 0.5 mL of 5 M phosphoric acid. Directly above this layer, pack a similar mixture of about 3 g of chromatographic siliceous earth and 2 mL of Ferric chloride–urea reagent. To an accurately weighed quantity of finely powdered Tablets, equivalent to 50 mg of aspirin, add 10 mL of chloroform, stir for 3 minutes, and transfer to the chromatographic adsorption column with the aid of 5 mL of chloroform. Pass 50 mL of 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-mL volumetric flask containing 20 mL of methanol and 4 drops of hydrochloric acid by passing two 10-mL portions of a 1 in 10 solution of glacial acetic acid in water-saturated ether, and then 30 mL of 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 150 µg of salicylic acid per mL. Pipet 5 mL of this solution into a 50-mL volumetric flask containing 10 mL of methanol, 2 drops of hydrochloric acid, and 10 mL of a 1 in 10 solution 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 306 nm, 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 711—
Medium:
water; 900 mL.
Apparatus 1:
80 rpm.
Time:
30 minutes.
Strongly basic,
anion-exchange resin—Mix a suitable quantity of anion-exchange resin with 10 volumes of dilute glacial acetic acid (1 in 50) and shake for 20 minutes. Allow the resin to settle, and decant the supernatant. Repeat the acetic acid washing four more times. Wash with water until 5.0 mL of the water wash gives a negligible response when substituted for 5.0 mL of the
Test solution, and carried through the
Determination of dissolved pentazocine below.
Test solution—
To a suitable 50-mL flask, add 0.4 g of
Strongly basic anion-exchange resin, and 25 mL of the solution under test. Shake by mechanical means for 15 minutes. 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 (1 in 50) containing 13 µg of
USP Pentazocine RS per mL.
PROCEDURE—
Transfer 5.0 mL portions of the Test solution, the Standard solution, and water to serve as the reagent blank, into three separate 125-mL separators. To each separator add 10 mL of a filtered 1 in 4000 solution of bromocresol purple in dilute glacial acetic acid (1 in 50) and 20.0 mL of chloroform. Insert the stopper, and shake gently for 1 minute, accurately timed. Allow the layers to separate, and determine the absorbances of the clear chloroform layers from the Standard solution and the Test solution in 1-cm cells at the wavelength of maximum absorbance at about 408 nm with a suitable spectrophotometer against the chloroform layer from the reagent blank. Determine the amount of pentazocine (C19H27NO) in the Test solution by comparison with the Standard solution.
Determination of dissolved aspirin—
STANDARD SOLUTION—
Prepare a solution containing 15 µg of
USP Salicylic Acid RS per mL of 0.1 N sodium hydroxide.
PROCEDURE—
Transfer 1.0 mL of the Test solution to a 25-mL volumetric flask containing 1.0 mL of sodium hydroxide solution (1 in 10), and swirl. Allow to stand for 10 minutes. Dilute with water to volume, and mix. Concomitantly determine the absorbances of the Test solution and of the Standard solution in 1-cm cells at the wavelength of maximum absorbance at about 296 nm with a suitable spectrophotometer, using 0.1 N sodium hydroxide as the blank. Calculate the quantity, in mg, of aspirin (C9H8O4) in the Test solution by 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 solution.
Tolerances—
Not less than 80% (Q) of the labeled amount of C19H27NO and not less than 70% (Q) of the labeled amount of C9H8O4 are dissolved in 30 minutes.
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 6 N hydrochloric acid (1:1), and allow to stand for 1 hour. 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 100 mm with slurry of the washed resin in a mixture of methanol and water (1:1). Wash the column with 25 mL of methanol and water (1:1).
Test solutions—
Weigh and finely powder not fewer than 20 Tablets. Transfer a portion of the freshly powdered Tablets, equivalent to about 25 mg of pentazocine and 650 mg of aspirin, accurately weighed, to a suitable 250-mL flask. Add 100.0 mL of a mixture of methanol and water (1:1), and shake by mechanical means for 20 minutes. Centrifuge a suitable quantity for 5 minutes. Transfer 25.0 mL of the clear supernatant to the prepared
Chromatographic column, followed by five 10-mL portions of the mixture of methanol and water (1:1), collecting the eluate in a 250-mL volumetric flask containing 10.0 mL of 2.5 N sodium hydroxide. Dilute with water to volume, and mix. Reserve this as
Test solution 1 for the
Determination of aspirin. Next pass through the column five 5-mL portions of a mixture of methanol and 6 N hydrochloric acid (1:1) followed by 10 mL of water. Collect the eluate in a 100-mL volumetric flask, dilute with water to volume, and use this as
Test solution 2 for the
Determination of pentazocine.
Determination of aspirin—
STANDARD SOLUTION—
Prepare a solution of
USP Salicylic Acid RS in 0.1 N sodium hydroxide having a known concentration of about 18 µg per mL.
PROCEDURE—
Pipet 4 mL of
Test solution 1 into a 100-mL volumetric flask, dilute with 0.1 N sodium hydroxide to volume, and mix (
Diluted test solution). Concomitantly determine the absorbances of the
Diluted test solution and the
Standard solution in 1-cm cells at the wavelength of maximum absorbance at about 296 nm with a suitable spectrophotometer, using 0.1 N sodium hydroxide as the blank. Calculate the quantity, in mg, of aspirin (C
9H
8O
4), in the portion of Tablets taken by the formula:
25C(180.16 / 138.12)(AU / AS),
in which
C is the concentration, in µg per mL, of
USP Salicylic Acid RS in the
Standard solution; (180.16/138.12) is the ratio of the molecular weight of aspirin to that of salicylic acid; and
AU and
AS are the absorbances of
Diluted test solution and the
Standard solution, respectively.
Determination of pentazocine—
STANDARD SOLUTION—
Prepare a solution of
USP Pentazocine RS in a mixture of water, methanol, and 6 N hydrochloric acid (6:1:1) having a known concentration of about 62.5 µg per mL.
PROCEDURE—
Concomitantly determine the absorbances of
Test solution 2 and the
Standard solution, in 1-cm cells at the wavelength of maximum absorbance at about 278 nm, with a suitable spectrophotometer, using the solvent for the
Standard solution as the blank. Calculate the quantity, in mg, of pentazocine (C
19H
27NO) in the portion of Tablets taken by the formula:
0.4C(AU / AS),
in which
C is the concentration, in µg per mL, of
USP Pentazocine RS in the
Standard solution; and
AU and
AS are the absorbances of
Test solution 2 and the
Standard solution, respectively.
Auxiliary Information—
Staff Liaison :
Clydewyn M. Anthony, Ph.D., Scientist
Expert Committee : (MDCCA05) Monograph Development-Cough Cold and Analgesics
USP29–NF24 Page 1673
Pharmacopeial Forum : Volume No. 28(6) Page 1847
Phone Number : 1-301-816-8139
Pentazocine Hydrochloride and Aspirin Tablets