Cocaine and Tetracaine Hydrochlorides and Epinephrine Topical Solution
»Cocaine and Tetracaine Hydrochlorides and Epinephrine Topical Solution contains not less than 3.6g and not more than 4.4g of Cocaine Hydrochloride,not less than 0.90g and not more than 1.10g of Tetracaine Hydrochloride,and not less than 20mg and not more than 30mg of Epinephrine in 100mLof Topical Solution prepared as follows (see Pharmaceutical Compounding—Nonsterile Preparations á795ñ):
Cocaine Hydrochloride 4.0g
Tetracaine Hydrochloride 1.0g
Epinephrine Injection (1:1000) 25.0mL
Benzalkonium Chloride 10mg
Edetate Disodium 6.4mg
Sodium Chloride Injection (0.9%) 35mL
Purified Water,a sufficient quantity
to make		 100mL
Dissolve the Cocaine and Tetracaine Hydrochlorides in about 25mLof 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 35mLof a solution containing 6.4mg 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 10mLof a solution containing 10mg of Benzalkonium Chloride.Combine the three solutions,add sufficient Purified Water to make the product measure 100mL,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.
pHá791ñ: between 4.0and 6.0.
Beyond-use date— Thirty days after the date on which it was compounded.
Compliance assay for tetracaine hydrochloride—
pH2.5Buffer— Dissolve 6.3g of monobasic potassium phosphate and 0.55g of sodium 1-octanesulfonate in water to make 1000mL,and adjust with phosphoric acid to a pHof 2.5.
Solution A— Combine 900mLofpH2.5Buffer and 100mLof acetonitrile in a suitable container.Pass the resulting solution through a filter having a 5-µm or finer porosity,and degas.
Solution B— Combine 700mLofpH2.5Buffer and 300mLof 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 ofSolution AandSolution Bas directed forChromatographic system.Make adjustments if necessary (seeSystem SuitabilityunderChromatography á621ñ).
Tetracaine standard preparation— Dissolve an accurately weighed quantity of USP Tetracaine Hydrochloride RSin water to obtain a solution having a known concentration of about 0.5mg per mL.
Assay preparation— Transfer 0.5mLof the Topical Solution to a 10-mLvolumetric flask,dilute with water to volume,and mix.
Chromatographic system(see Chromatography á621ñ)— 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 1mLper 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 theTetracaine standard preparation,and record the peak responses as directed forProcedure: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 20µL)of theTetracaine standard preparation and theAssay preparation into the chromatograph,record the chromatograms,and measure the tetracaine peak responses.Calculate the quantity,in g,of tetracaine hydrochloride (C15H24N2O2·HCl)in 100mLof the Topical Solution taken by the formula:
2C(rU/rS),
in whichCis the concentration,in mg per mL,of USP Tetracaine Hydrochloride RSin theTetracaine standard preparation;andrUandrSare the peak responses obtained from theAssay preparation and theTetracaine standard preparation,respectively.
Compliance assay for cocaine hydrochloride—
pH2.5Buffer,Solution A,Solution B,Tetracaine standard preparation,Assay preparation,and Chromatographic system— Proceed as directed in theCompliance assay for tetracaine hydrochloride.
Cocaine standard preparation— Dissolve an accurately weighed quantity of USP Cocaine Hydrochloride RSquantitatively in water to obtain a solution having a known concentration of about 2.0mg per mL.
Procedure— Separately inject equal volumes (about 20µL)of theCocaine standard preparation and theAssay preparation into the chromatograph,record the chromatograms,and measure the cocaine peak responses.Calculate the quantity,in g,of cocaine hydrochloride (C17H21NO4·HCl)in 100mLof the Topical Solution taken by the formula:
2C(rU/rS),
in whichCis the concentration,in mg per mL,of USP Cocaine Hydrochloride RSin theCocaine standard preparation;andrUandrSare the peak responses obtained from theAssay preparation and theCocaine standard preparation,respectively.
Compliance assay for epinephrine—
pH2.5Buffer,Solution A,Solution B,Tetracaine standard preparation,Assay preparation,and Chromatographic system— Proceed as directed in theCompliance assay for tetracaine hydrochloride.
Epinephrine standard preparation— Transfer about 3mg of USP Epinephrine Bitartrate RS,accurately weighed,to a 25-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.Transfer 4.0mLof this solution to a 25-mLvolumetric flask,dilute with water to volume,and mix.
Procedure— Separately inject equal volumes (about 20µL)of theEpinephrine standard preparation and theAssay preparation into the chromatograph,record the chromatograms,and measure the epinephrine peak responses.Calculate the quantity,in g,of epinephrine (C9H13NO3)in 100mLof the Topical Solution taken by the formula:
(183.20/333.29)2C(rU/rS),
in which 183.20and 333.29are the molecular weights of epinephrine and epinephrine bitartrate,respectively;Cis the concentration,in mg per mL,of USP Epinephrine Bitartrate RSin theEpinephrine standard preparation;andrUandrSare the peak responses obtained from theAssay preparation and theEpinephrine standard preparation,respectively.
Auxiliary Information— Staff Liaison:Claudia C.Okeke,Ph.D.,Associate Director
Expert Committee:(CRX)Compounding Pharmacy
USP28–NF23Page 532
Pharmacopeial Forum:Volume No.28(2)Page 270
Phone Number:1-301-816-8243