USP33-75ppm含甲醛方法和指标

Tyloxapol Phenol, 4-(1,1,3,3-tetramethylbutyl)-, polymer with formaldehyde and oxirane. p-(1,1,3,3-Tetramethylbutyl)phenol polymer with ethylene oxide and formaldehyde [25301- 02-4]. » Tyloxapol is a nonionic liquid polymer of the alkyl aryl polyether alcohol type. NOTE— Precautions should be exercised to prevent contact of Tyloxapol with metals. Packaging and storage— Preserve in tight containers. USP REFERENCE STANDARDS 11 — USP Tyloxapol RS . IDENTIFICATION, Infrared Absorption 197F : on undried specimen. Cloud point— Transfer 1.0 g of it, previously mixed, to a 150-mL beaker. Add 100.0 mL of water, and mix until solution is effected. Warm the solution while mixing: transient turbidity may be observed as the solution is warmed. Determine the temperature at which the mixture becomes completely turbid: the cloud point is between 92 and 97 . PH 791 : between 4.0 and 7.0, in a solution (1 in 20). RESIDUE ON IGNITION 281 : not more than 1.0%. Free phenol— To 10 mL of a solution (1 in 100) add 1 mL of bromine TS, and mix: no cloudiness or precipitation is observed immediately. Limit of anionic detergents— Mix 20 mL of a solution (1 in 100) with 30 mL of water in a 125- mL separator. In a second 125-mL separator mix 50 mL of water and 1 mL of a solution of sodium lauryl sulfate containing 150 µg per mL. To both separators add 2 drops of 3 N hydrochloric acid, 1 drop of methylene blue solution (1 in 25), and 25 mL of chloroform. Shake both separators gently for 2 minutes, allow to stand for 10 minutes, and transfer the chloroform layers to individual separators. Wash the chloroform extracts with separate 25-mL portions of water, transfer the chloroform solutions to matched 50-mL color-comparison tubes, and view downward over a white surface: the chloroform solution from the Tyloxapol preparation is not darker than that from the sodium lauryl sulfate preparation, corresponding to not more than 0.075% of anionic detergents (as sodium lauryl sulfate). Limit of ethylene oxide— Standard preparation— [CAUTION—ETHYLENE OXIDE IS TOXIC AND FLAMMABLE. PREPARE IN A WELL-VENTILATED HOOD, USING GREAT CARE.] Transfer 25 mL of dimethylformamide to a 50-mL volumetric flask, and weigh accurately. Add about 0.5 mL of ethylene oxide, and mix. Reweigh to obtain the weight of ethylene oxide by difference. Dilute with dimethylformamide to volume, and mix. Dilute a portion of this solution with dimethylformamide to obtain a Standard preparation having a known concentration of about 10 ppm of ethylene oxide. Test preparation— Transfer 1 g of Tyloxapol, accurately weighed, to a glass-stoppered, 5-mL graduated cylinder. Dilute with dimethylformamide to 2.0 mL, and mix. Chromatographic system (see Chromatography 621 )—The gas chromatograph is equipped with a flame-ionization detector and a 1.8-m × 2-mm glass column containing 5% phase G16 on support S12. The injection port is maintained at about 200 and the detector at about 250 . The column temperature is programmed as follows. The temperature is maintained at 50 for 3 minutes, then increased to 200 at a rate of 25 per minute, and held at 200 for 5 minutes. Helium is used as the carrier gas at a flow rate of about 25 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not greater than 10%. Procedure— Separately inject equal volumes (about 3 µL) of the Standard preparation and the Test preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in ppm, of ethylene oxide in the portion of Tyloxapol taken by the formula: 2(C / W)( r U / r S) in which C is the concentration, in µg per mL, of ethylene oxide in the Standard preparation, W is the weight, in g, of Tyloxapol taken in the Test preparation, and r U and r S are the ethylene oxide peak responses obtained from the Test preparation and the Standard preparation, respectively: not more than 10 ppm of ethylene oxide are found. Limit of formaldehyde — Standard preparations— Weigh 2.7 g of formaldehyde solution into a 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 1.0 mL of this solution to a second 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 10.0 mL of this second solution to a third 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 750 µL of this solution to a 25-mL volumetric flask containing 5 mL of a solution of isopropyl alcohol (4 in 10). Test preparation— Transfer 2.0 g of Tyloxapol to a 10-mL volumetric flask, and dissolve in a solution of isopropyl alcohol (4 in 10), then dilute with a solution of isopropyl alcohol (4 in 10) to volume, and mix. Transfer 500 µL of this solution to a 25-mL volumetric flask containing 5 mL of isopropyl alcohol solution (4 in 10). Procedure— To the Standard preparation, the Test preparation, and a blank, prepared by placing 5 mL of isopropyl alcohol solution (4 in 10) in a 25-mL volumetric flask, add 500 µL of phenylhydrazine hydrochloride solution (7.5 in 100), mix, and allow to stand for 10 ± 1 minutes. Add 300 µL of potassium ferricyanide solution (1 in 20) to each flask, mix, and allow to stand for 5 minutes ± 30 seconds. Then add 2.0 mL of 2.5 N sodium hydroxide to each, mix, and allow to stand for 4 ± 1 minutes. Dilute each flask with isopropyl alcohol solution (4 in 10) to volume, mix, and after 10 ± 3 minutes determine the absorbances of the preparations, in 1-cm cells, at the wavelength of maximum absorbance at about 520 nm, with a suitable spectrophotometer, using the blank to set the instrument. The absorbance of the solution from the Test preparation does not exceed that of the solution from the Standard preparation, corresponding to not more than 0.0075% of formaldehyde . Absence of cationic detergents— Place 10 mL of a solution (1 in 100) in a glass-stoppered, 50-mL graduated cylinder, and make distinctly alkaline to litmus with sodium carbonate TS (about 1 mL). Add 4 mL of aqueous bromophenol blue solution (1 in 2500), mix, and add 10 mL of a 1 in 10 solvent mixture of ethylene dichloride in toluene. Shake gently, and allow the layers to separate: no blue color is observed in the organic solvent layer. Auxiliary Information— Please check for your question in the FAQs before contacting USP. USP32–NF27 Page 3828 Topic/Question Contact Expert Committee Monograph Hong Wang, Ph.D. Scientist 1-301-816-8351 (EM205) Excipient Monographs 2 Reference Standards Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org