U.S. PHARMACOPEIA

Search USP29  
Phenylephrine Hydrochloride
Click to View Image
C9H13NO2·HCl 203.67

Benzenemethanol, 3-hydroxy--[(methylamino)methyl]-, hydrochloride (R)-.
()-m-Hydroxy--[(methylamino)methyl]benzyl alcohol hydrochloride [61-76-7].
» Phenylephrine Hydrochloride contains not less than 97.5 percent and not more than 102.5 percent of C9H13NO2·HCl, calculated on the dried basis.
Packaging and storage— Preserve in tight, light-resistant containers. Store at 25, excursions permitted between 15and 30.
Identification—
B: A solution (1 in 100) responds to the tests for Chloride 191.
Melting range 741: between 140 and 145.
Specific rotation 781S: between 42 and 47.5.
Test solution: 50 mg per mL, in water.
Loss on drying 731— Dry it at 105 for 2 hours: it loses not more than 1.0% of its weight.
Residue on ignition 281: not more than 0.2%.
Sulfate 221— A solution of 50 mg in 25 mL of water shows no more turbidity than corresponds to 0.10 mL of 0.020 N sulfuric acid (0.20%).
Limit of ketones— Dissolve 200 mg in 1 mL of water, add 2 drops of sodium nitroferricyanide TS, then add 1 mL of 1 N sodium hydroxide, followed by 0.6 mL of glacial acetic acid: the color of the final solution is not deeper than that obtained in a control solution prepared with 1 mL of dilute acetone (1 in 2000).
Chromatographic purity—
Standard preparations— Dissolve an accurately weighed quantity of USP Phenylephrine Hydrochloride RS in methanol to obtain a solution having a known concentration of 1 mg per mL. Quantitatively dilute with methanol to obtain Standard preparations having the following compositions:
Standard
Preparation		 Dilution Concentration
(µg RS
per mL)		 Percentage (%,
for comparison
with test
specimen)
A (1 in 2) 500 1.0
B (1 in 4) 250 0.5
C (1 in 10) 100 0.2
D (1 in 20) 50 0.1
Test preparation— Dissolve an accurately weighed quantity of Phenylephrine Hydrochloride in methanol to obtain a solution containing 50 mg per mL.
Procedure— Apply separately 5 µL of the Test preparation and 5 µL of each Standard preparation to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Position the plate in a chromatographic chamber and develop the chromatograms in a solvent system consisting of a mixture of n-butyl alcohol, water, and formic acid (7:2:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow the solvent to evaporate in warm, circulating air. Examine the plate under short-wavelength UV light. Then spray the plate with a saturated solution of p-nitrobenzenediazonium tetrafluoroborate followed by sodium carbonate solution (1 in 10). Compare the intensities of any secondary spots observed in the chromatogram of the Test preparation with those of the principal spots in the chromatograms of the Standard preparations: the sum of the intensities of secondary spots obtained from the Test preparation corresponds to not more than 1.0% of related compounds, with no single impurity corresponding to more than 0.5%.
Chloride content— Dissolve about 300 mg, accurately weighed, in 5 mL of water. Add 5 mL of glacial acetic acid and 50 mL of methanol, then add eosin Y TS, and titrate with 0.1 N silver nitrate VS. Each mL of 0.1 N silver nitrate is equivalent to 3.545 mg of Cl. Not less than 17.0% and not more than 17.7% of Cl is found, calculated on the dried basis.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 100 mg of Phenylephrine Hydrochloride, accurately weighed, in 20 mL of water contained in an iodine flask, add 50.0 mL of 0.1 N bromine VS, then add 5 mL of hydrochloric acid, and immediately insert the stopper. Shake the flask, and allow to stand for 15 minutes. Introduce quickly 10 mL of potassium iodide solution (1 in 10), allow to stand for 5 minutes, shake thoroughly, remove the stopper, and rinse it and the neck of the flask with a small quantity of water into the flask. Titrate the liberated iodine with 0.1 N sodium thiosulfate VS, adding 3 mL of starch TS as the endpoint is approached. Perform a blank determination (see Residual Titrations under Titrimetry 541). Each mL of 0.1 N bromine is equivalent to 3.395 mg of C9H13NO2·HCl.
Auxiliary Information— Staff Liaison : Clydewyn M. Anthony, Ph.D., Scientist
Expert Committee : (MDCCA05) Monograph Development-Cough Cold and Analgesics
USP29–NF24 Page 1712
Pharmacopeial Forum : Volume No. 29(6) Page 1964
Phone Number : 1-301-816-8139