U.S. PHARMACOPEIA

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Cocaine and Tetracaine Hydrochlorides and Epinephrine Topical Solution
» Cocaine and Tetracaine Hydrochlorides and Epinephrine Topical Solution contains not less than 3.6 g and not more than 4.4 g of Cocaine Hydrochloride, not less than 0.90 g and not more than 1.10 g of Tetracaine Hydrochloride, and not less than 20 mg and not more than 30 mg of Epinephrine in 100 mL of Topical Solution prepared as follows (see Pharmaceutical Compounding—Nonsterile Preparations 795):
Cocaine Hydrochloride 4.0 g
Tetracaine Hydrochloride 1.0 g
Epinephrine Injection (1:1000) 25.0 mL
Benzalkonium Chloride 10 mg
Edetate Disodium 6.4 mg
Sodium Chloride Injection (0.9%) 35 mL
Purified Water, a sufficient quantity
to make		 100 mL
Dissolve the Cocaine and Tetracaine Hydrochlorides in about 25 mL of Purified Water, and add the Epinephrine Injection (1:1000). Separately dissolve an accurately weighed quantity of Edetate Disodium in Sodium Chloride Injection (0.9%), and dilute quantitatively, and stepwise if necessary, with Sodium Chloride Injection (0.9%) to obtain 35 mL of a solution containing 6.4 mg of Edetate Disodium. Similarly, and separately, dissolve an accurately weighed quantity of Benzalkonium Chloride in Purified Water (or use an accurately measured volume of Benzalkonium Chloride Solution), and dilute quantitatively, and stepwise if necessary, with Purified Water to obtain 10 mL of a solution containing 10 mg of Benzalkonium Chloride. Combine the three solutions, add sufficient Purified Water to make the product measure 100 mL, and mix to produce the Topical Solution.
Packaging and storage— Preserve in sterile, tight, light-resistant containers. Store in a refrigerator.
Labeling— Label it to state that it is intended for external use only and that it is not to be used if a precipitate is present. The label states that it is to be protected from light.
pH 791: between 4.0 and 6.0.
Beyond-use date— Thirty days after the date on which it was compounded.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Compliance assay for tetracaine hydrochloride—
pH 2.5 Buffer— Dissolve 6.3 g of monobasic potassium phosphate and 0.55 g of sodium 1-octanesulfonate in water to make 1000 mL, and adjust with phosphoric acid to a pH of 2.5.
Solution A— Combine 900 mL of pH 2.5 Buffer and 100 mL of acetonitrile in a suitable container. Pass the resulting solution through a filter having a 5-µm or finer porosity, and degas.
Solution B— Combine 700 mL of pH 2.5 Buffer and 300 mL of acetonitrile in a suitable container. Pass the resulting solution through a filter having a 5-µm or finer porosity, and degas.
Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
Tetracaine standard preparation— Dissolve an accurately weighed quantity of USP Tetracaine Hydrochloride RS in water to obtain a solution having a known concentration of about 0.5 mg per mL.
Assay preparation— Transfer 0.5 mL of the Topical Solution to a 10-mL volumetric flask, dilute with water to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 30-cm column that contains 10-µm packing L1. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows.
Time
(minutes)		 Solution A
(%)		 Solution B
(%)		 Elution
0 100 0 equilibration
0–5 100 0 isocratic
5–10 100®0 0®100 linear gradient
10–34 0 100 isocratic
24–25 0®100 100®0 linear gradient
25–75 100 0 isocratic
Chromatograph the Tetracaine standard preparation, and record the peak responses as directed for Procedure: the tailing factor for the analyte peak is not more than 1.5; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20 µL) of the Tetracaine standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the tetracaine peak responses. Calculate the quantity, in g, of tetracaine hydrochloride (C15H24N2O2·HCl) in 100 mL of the Topical Solution taken by the formula:
2C(rU / rS),
in which C is the concentration, in mg per mL, of USP Tetracaine Hydrochloride RS in the Tetracaine standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Tetracaine standard preparation, respectively.
Compliance assay for cocaine hydrochloride—
pH 2.5 Buffer, Solution A, Solution B, Tetracaine standard preparation, Assay preparation, and Chromatographic system— Proceed as directed in the Compliance assay for tetracaine hydrochloride.
Cocaine standard preparation— Dissolve an accurately weighed quantity of USP Cocaine Hydrochloride RS quantitatively in water to obtain a solution having a known concentration of about 2.0 mg per mL.
Procedure— Separately inject equal volumes (about 20 µL) of the Cocaine standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the cocaine peak responses. Calculate the quantity, in g, of cocaine hydrochloride (C17H21NO4·HCl) in 100 mL of the Topical Solution taken by the formula:
2C(rU / rS),
in which C is the concentration, in mg per mL, of USP Cocaine Hydrochloride RS in the Cocaine standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Cocaine standard preparation, respectively.
Compliance assay for epinephrine—
pH 2.5 Buffer, Solution A, Solution B, Tetracaine standard preparation, Assay preparation, and Chromatographic system— Proceed as directed in the Compliance assay for tetracaine hydrochloride.
Epinephrine standard preparation— Transfer about 3 mg of USP Epinephrine Bitartrate RS, accurately weighed, to a 25-mL volumetric flask, dissolve in and dilute with water to volume, and mix. Transfer 4.0 mL of this solution to a 25-mL volumetric flask, dilute with water to volume, and mix.
Procedure— Separately inject equal volumes (about 20 µL) of the Epinephrine standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the epinephrine peak responses. Calculate the quantity, in g, of epinephrine (C9H13NO3) in 100 mL of the Topical Solution taken by the formula:
(183.20/333.29)2C(rU / rS),
in which 183.20 and 333.29 are the molecular weights of epinephrine and epinephrine bitartrate, respectively; C is the concentration, in mg per mL, of USP Epinephrine Bitartrate RS in the Epinephrine standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Epinephrine standard preparation, respectively.
Auxiliary Information— Staff Liaison : Claudia C. Okeke, Ph.D., Associate Director
Expert Committee : (CRX05) Compounding Pharmacy05
USP29–NF24 Page 579
Pharmacopeial Forum : Volume No. 28(2) Page 270
Phone Number : 1-301-816-8243