Epinephryl Borate Ophthalmic Solution
1,3,2-Benzodioxaborole-5-methanol, 2-hydroxy--[(methylamino)methyl]-, (R)-.
()-3,4-Dihydroxy--[(methylamino)methyl]benzyl alcohol, cyclic 3,4-ester with boric acid [5579-16-8].
» Epinephryl Borate Ophthalmic Solution is a sterile solution in water of Epinephrine as a borate complex. It contains an amount of epinephryl borate (C9H12BNO4) equivalent to not less than 90.0 percent and not more than 115.0 percent of the labeled amount of epinephrine (C9H13NO3). It contains a suitable antibacterial agent and one or more suitable preservatives and buffering agents.
Packaging and storage Preserve in small, well-filled, tight, light-resistant containers.
Labeling The label indicates that the Ophthalmic Solution is not to be used if its color is pinkish or darker than slightly yellow or if it contains a precipitate.
Color and clarity
Standard solution Transfer 2.0 mL of 0.100 N iodine VS to a 500-mL volumetric flask, dilute with water to volume, and mix.
Procedure Visually examine a portion of the Ophthalmic Solution (Test solution) in a suitable clear glass test tube against a white background: it is not pinkish, and it contains no precipitate. If any yellow color is observed in the Test solution, concomitantly determine the absorbances of the Test solution and the Standard solution in 1-cm cells with a suitable spectrophotometer set at 460 nm: the absorbance of the Test solution does not exceed that of the Standard solution.
A: To 5 mL of pH 4.0 acid phthalate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions) add 0.5 mL of Ophthalmic Solution and 1 mL of 0.1 N iodine. Mix, allow to stand for 5 minutes, and add 2 mL of 0.1 N sodium thiosulfate: a deep red color is produced.
B: To 5 mL in a porcelain evaporating dish add 5 drops of sulfuric acid and 5 mL of methanol: the ignited mixture burns with a green-bordered flame.
Sterility 71: meets the requirements.
pH 791: between 5.5 and 7.6.
Assay Transfer an accurately measured volume of Ophthalmic Solution, equivalent to about 100 mg of epinephrine, to a 250-mL separator. Dilute with water to 30 mL, and adjust with dilute hydrochloric acid (1 in 12) to a pH of 4.0 ± 0.2. Add 25 mL of carbon tetrachloride, shake vigorously for 1 minute, allow the phases to separate, and discard the carbon tetrachloride washing. In the same manner, wash with two additional 25-mL portions of carbon tetrachloride, and discard the washings. Rinse the stopper and the mouth of the separator with 2 to 3 mL of water such that the rinsings enter the separator and combine with the solution under assay. Add 0.2 mL of starch TS, and, while swirling the separator, add iodine and potassium iodide TS 1 dropwise until the blue color persists. Immediately add a volume of 0.1 N sodium thiosulfate just sufficient to discharge the blue color. [noteProceed with the assay from this point without delay. ]
Add 2.10 g of sodium bicarbonate through a dry powder funnel to prevent the powder from coming in contact with the mouth of the separator, and swirl to dissolve most of the solid. By means of a syringe fitted with a suitable pipet, rapidly inject 1.0 mL of acetic anhydride directly into the contents of the separator. Swirl the unstoppered separator gently for 3 minutes to allow carbon dioxide to escape. Insert the stopper, and shake gently until the evolution of carbon dioxide has ceased (7 to 10 minutes), releasing the pressure through the stopcock as necessary. Allow to stand for 5 minutes. Extract with six 25-mL portions of chloroform, shaking for 1 minute each time, filtering each extract through a small pledget of chloroform-saturated cotton and collecting the extracts in a 400-mL beaker. Add several glass beads, and evaporate on a steam bath to about 3 mL. With the aid of 15 to 20 mL of chloroform, transfer the residue to a tared 50-mL beaker, and evaporate on the steam bath to dryness. Dry the residue at 105 for 30 minutes, cool in a desiccator, and weigh the triacetylepinephrine so obtained. Transfer 10.0 mL of chloroform to the beaker, and gently swirl to dissolve the residue, dislodging the semisolid residue from the glass surface, if necessary, with a small metal spatula. Determine the angular rotation of the solution in a 100-mm polarimeter tube.
Calculate the quantity, in mg, of epinephrine (C9H13NO3) in the volume of Ophthalmic Solution taken by the formula:
(183.20/309.32)(W)(0.5 + 0.5R/93)
in which 183.20 and 309.32 are the molecular weights of epinephrine and triacetylepinephrine, respectively; W is the weight, in mg, of the isolated triacetylepinephrine; and R is the specific rotation, in degrees, of the triacetylepinephrine solution.
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USP35NF30 Page 3057Pharmacopeial Forum: Volume No. 30(4) Page 1192