Pharm-Rx LABETALOL HCl

Labetalol Hydrochloride contains not less than 97.5 percent and not more than 101.0 percent of C₁₉H₂₄N₂O₃ · HCl, calculated on the dried basis. Packaging and storage—Preserve in tight, light-resistant containers. Store at 25°, excursions permitted between 15° and 30°. USP Reference standards á11ñ— USP Labetalol Hydrochloride RS Identification— Change to read: A: Spectroscopic Identification Tests á197ñ, Infrared Spectroscopy: 197M (CN 1-May-2020). B: It responds to the tests for Chloride á191ñ. pH á791ñ: between 4.0 and 5.0, in a solution (1 in 100). Loss on drying á731ñ: Dry it in a vacuum at 105° for 4 hours: it loses not more than 1.0% of its weight. Residue on ignition á281ñ: not more than 0.1%. Chromatographic purity— Detection reagent—Transfer 2.5 g of cadmium acetate to a 500-mL volumetric flask, add 10 mL of glacial acetic acid, dilute with alcohol to volume, and mix. Just prior to use, prepare a 0.2 in 100 solution of ninhydrin in the cadmium acetate solution for use as the Detection reagent. Solvent mixture—Prepare a solution of methanol and water (4:1), and mix. Ammonium chloride reference solution—Dissolve 60 mg of ammonium chloride in 10.0 mL of water, and mix. Standard stock solution—Dissolve USP Labetalol Hydrochloride RS in Solvent mixture, and mix to obtain a solution having a known concentration of 40 mg per mL. Standard solution 1—Quantitatively dilute a portion of the Standard stock solution with Solvent mixture to obtain a solution having a known concentration of 0.2 mg per mL. Standard solution 2—Quantitatively dilute a portion of the Standard solution 1 with Solvent mixture to obtain a solution having a known concentration of 0.1 mg per mL. Test solution—Dissolve 200 mg of Labetalol Hydrochloride in 5.0 mL of Solvent mixture, and mix. Procedure I—Apply separately 5-μL portions of the Standard stock solution, Standard solution 1, Standard solution 2, and the Test solution to a suitable thin-layer chromatographic plate (see Chromatography á621ñ) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatograms in a solvent system consisting of a mixture of dichloromethane, methanol, and ammonium hydroxide (15:5:1) 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. Examine the plate under short-wavelength UV light: the R F value of the principal spot from the Test solution corresponds to that of the principal spot from the Standard stock solution. Spray the plate with Detection reagent, heat the plate at 105° for 15 minutes, cool to room temperature, and examine the chromatogram: no individual secondary spot observed in the chromatogram of the Test solution is greater in size or intensity than the principal spot observed in the chromatogram of Standard solution 1 (0.5% each). [NOTE—The spots appear as dark orange spots on a light orange to yellow background. A “negative image” spot (white) near the origin may be observed in the chromatogram of the Test solution. This is due to the formation of ammonium chloride during the chromatographic procedure and may be ignored.] Procedure II—Apply separately 10-μL portions of the Ammonium chloride reference solution, the Standard stock solution, Standard solution 1, Standard solution 2, and the Test solution to a suitable thin-layer chromatographic plate (see Chromatography á621ñ), coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatograms in a solvent system consisting of a mixture of ethyl acetate, isopropyl alcohol, water, and ammonium hydroxide (25:15:8:2) 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. Examine the plate under short-wavelength UV light: no individual secondary spot (other than that due to ammonium chloride) observed in the chromatogram of the Test solution is greater in size or intensity than the principal spot observed in the chromatogram of Standard solution 1 (0.5% each). Total impurities—The sum of the intensities of all secondary spots (other than those due to ammonium chloride) observed in the chromatograms of the Test solution from both Procedure I and Procedure II does not exceed 1.0%. Diastereoisomer ratio— 1-Butaneboronic acid solution—Dissolve 1-butaneboronic acid in pyridine, previously dried over a suitable molecular sieve, and mix to obtain a solution having a known concentration of 20 mg per mL. System suitability solution—Dissolve an accurately weighed quantity of USP Labetalol Hydrochloride RS in 1-Butaneboronic acid solution, and dilute quantitatively and stepwise with 1-Butaneboronic acid solution to obtain a solution having a known concentration of about 1.4 mg of USP Labetalol Hydrochloride RS per mL. Allow the solution to stand at room temperature for 20 minutes before using. Test solution—Transfer about 1 mg of Labetalol Hydrochloride to a 1-mL reaction vial, add 0.7 mL of 1-Butaneboronic acid solution, and mix until the labetalol hydrochloride is completely dissolved. Allow the solution to stand at room temperature for 20 minutes before using. Chromatographic system (see Chromatography á621ñ)—The gas chromatograph is equipped with a flame-ionization detector and a 2-mm × 1.8-m glass column packed with 10% phase G3 on 100- to 120-mesh support S1AB. The column temperature is maintained at about 320°, and the injection port and the detector block temperatures are maintained at about 340°. Nitrogen is used as the carrier gas at the flow rate of about 30 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for the diastereoisomer B 1-butaneboronate derivative and 1.0 for the diastereoisomer A 1-butaneboronate derivative; the resolution, R, between the diastereoisomer A 1-butaneboronate derivative and diastereoisomer B 1-butaneboronate derivative peaks is not less than 1.5; and the relative standard deviation of the ratios of the peak areas of the 1 Printed on: Wed Mar 27 2024, 04:33:54 AM(EST) Status: Currently Official on 27-Mar-2024 DocId: GUID-370BC3B4-88DD-4B88-A902-5F8921F921D5_4_en-US Printed by: Ann Smith Official Date: Official as of 01-May-2020 Document Type: USP @2024 USPC Do Not Distribute DOI Ref: k1h65 DOI: https://doi.org/10.31003/USPNF_M44030_04_01 https://online.uspnf.com/uspnf/document/1_GUID-370BC3B4-88DD-4B88-A902-5F8921F921D5_4_en-US 1/2 Official