(klor'' oh proe' kane hye'' droe klor' ide).
Benzoic acid, 4-amino-2-chloro-, 2-(diethylamino)ethyl ester, monohydrochloride.
2-(Diethylamino)ethyl 4-amino-2-chlorobenzoate monohydrochloride [3858-89-7].
» Chloroprocaine Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C13H19ClN2O2·HCl, calculated on the dried basis.
Packaging and storage Preserve in well-closed containers.
USP Reference standards 11
Solution: 10 µg per mL.
Medium: pH 4.5 buffer solution [prepared by dissolving 13.61 g of monobasic potassium phosphate in 750 mL of water, adjusting to a pH of 4.5 ± 0.1 with potassium hydroxide solution (1 in 180) and diluting with water to 1000 mL]. Absorptivities at 290 nm, calculated on the dried basis, do not differ by more than 3.0%.
C: It meets the requirements of the tests for Chloride 191.
Melting range, Class I 741: between 173 and 176.
Acidity Dissolve 1.0 g in 25 mL of water, add 2 drops of methyl red TS, and titrate with 0.020 N sodium hydroxide: not more than 1.8 mL is required to produce a yellow color.
Loss on drying 731 Dry about 500 mg, accurately weighed, at 105 for 2 hours: it loses not more than 1.0% of its weight.
Residue on ignition 281: not more than 0.2%.
4-Amino-2-chlorobenzoic acid Using the chromatograms obtained as directed for the Assay, calculate the percentage of 4-amino-2-chlorobenzoic acid (C7H6ClNO2) in the Chloroprocaine Hydrochloride taken by the formula:
10,000(C / W)(rU / rS)in which C is the concentration, in mg per mL, of 4-amino-2-chlorobenzoic acid in the Standard preparation; W is the quantity, in mg, of Chloroprocaine Hydrochloride taken to prepare the Assay preparation; and rU and rS are the 4-amino-2-chlorobenzoic acid peak responses obtained from the Assay preparation and the Standard preparation, respectively: not more than 0.625% is found.
Mobile phase Dissolve 800 mg of sodium 1-heptanesulfonate in 740 mL of water, add 200 mL of acetonitrile, 50 mL of methanol, and 10 mL of glacial acetic acid, and mix. Filter and degas this solution. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard 4-amino-2-chlorobenzoic acid solution Dissolve an accurately weighed quantity of recrystallized 4-amino-2-chlorobenzoic acid in methanol to obtain a solution having a known concentration of about 0.2 mg per mL.
Standard preparation Transfer about 50 mg of USP Chloroprocaine Hydrochloride RS, accurately weighed, to a 50-mL volumetric flask containing 5.0 mL of Standard 4-amino-2-chlorobenzoic acid solution, add 15 mL of methanol, swirl to dissolve, dilute with water to volume, and mix. This solution contains about 1 mg of USP Chloroprocaine Hydrochloride RS and 0.02 mg of 4-amino-2-chlorobenzoic acid per mL.
System suitability solution Mix equal volumes of Standard 4-amino-2-chlorobenzoic acid solution and Standard preparation.
Assay preparation Transfer about 100 mg of Chloroprocaine Hydrochloride, accurately weighed, to a 100-mL volumetric flask, dissolve in 40 mL of methanol, dilute with water to volume, and mix.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 278-nm detector and a 3.9-mm × 30-cm column containing packing L1. The flow rate is about 2 mL per minute. Chromatograph the System suitability solution, and record the responses as directed for Procedure: the relative retention times are about 0.35 for 4-amino-2-chlorobenzoic acid and 1.0 for chloroprocaine; and the resolution, R, between 4-amino-2-chlorobenzoic acid and chloroprocaine is not less than 5.0. Chromatograph the Standard preparation, and record the responses as directed for Procedure: the relative standard deviation determined from chloroprocaine obtained from replicate injections is not more than 1.0%.
Procedure Separately inject equal volumes (about 5 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses for 4-amino-2-chlorobenzoic acid and chloroprocaine. Calculate the quantity, in mg, of C13H19ClN2O2·HCl in the portion of Chloroprocaine Hydrochloride taken by the formula:
100C(rU / rS)in which C is the concentration, in mg per mL, of USP Chloroprocaine Hydrochloride RS in the Standard preparation; and rU and rS are the chloroprocaine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 2629Pharmacopeial Forum: Volume No. 29(5) Page 1438