4104 Levonorgestrel / Official Monographs USP 36

Column: 4-mm × 15-cm; packing L7 Identification— Flow rate: 1 mL/min A: Infrared Absorption 〈197K〉—Obtain the test specimen Injection size: 100 µL as follows. Dissolve 50 mg in 25 mL of water in a 125-mL System suitability separator. Add 2 mL of 6 N ammonium hydroxide, extract Sample: Standard solution with 25 mL of chloroform, and filter the chloroform extract [NOTE—The relative retention times for ethinyl estradiol through a layer of 4 g of granular anhydrous sodium sulfate and levonorgestrel are about 0.7 and 1.0, supported on glass wool into a 125-mL conical flask. Evapo- respectively.] rate the chloroform extract on a steam bath with the aid of Suitability requirements a stream of nitrogen to dryness. Dissolve the residue in 1 mL Relative standard deviation: NMT 3.0% of acetone, and evaporate to dryness. Dry in vacuum at 90° Analysis for 1 hour. Proceed as directed with the dried levorphanol Samples: Standard solution and Sample solution so obtained and a similar preparation of USP Levorphanol Calculate the percentage of C21H28O2 and C20H24O2 Tartrate RS. dissolved: B: Ultraviolet Absorption 〈197U〉—

Result = (rU/rS) × (CS/CU) × 100 Solution: 130 µg per mL. Medium: 0.1 N hydrochloric acid. rU = peak response of the corresponding analyte Absorptivities at 279 nm, calculated on the anhydrous ba- from the Sample solution sis, do not differ by more than 3.0%. rS = peak response of the corresponding analyte Specific rotation 〈781S〉: between −14.7° and −16.3°. from the Standard solution Test solution: 30 mg per mL, in water. Heat on a water CS = concentration of the appropriate USP Reference Standard in the Standard solution bath or sonicate to dissolve 750 mg in 20 mL of water in a (µg/mL) 25-mL volumetric flask, dilute with water to volume, and mix. CU = nominal concentration of the corresponding analyte in the Sample solution (µg/mL) Water, Method I 〈921〉: between 7.0% and 9.0%. Tolerances Residue on ignition 〈281〉: not more than 0.1%. Uncoated Tablets: NLT 80% (Q) of the labeled Ordinary impurities 〈466〉— amount of C21H28O2, and 75% (Q) of the labeled Test solution: water. amount of C20H24O2 is dissolved. Coated Tablets: NLT 60% (Q) of the labeled amount Standard solution: water. of C21H28O2 and C20H24O2 is dissolved. Eluant: a mixture of hexanes, dehydrated alcohol, and • UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the ammonium hydroxide (80:25:1). requirements Visualization: 17; then view immediately under short- Sample solution: Place 1 Tablet in a 40-mL centrifuge wavelength UV light. tube, add 10.0 mL of Mobile phase, and proceed as di- Assay—Dissolve about 900 mg of sample, accurately rected in the Assay. weighed, in 85 mL of glacial acetic acid, warming slightly if ADDITIONAL REQUIREMENTS necessary. Titrate with 0.1 N perchloric acid VS and deter- mine the endpoint potentiometrically. Perform a blank de- • PACKAGING AND STORAGE: Preserve in well-closed containers. termination and make any nececssary corrections. Each mL of 0.1 N perchloric acid consumed by the sample is equiva- • USP REFERENCE STANDARDS 〈11〉 USP Ethinyl Estradiol RS lent to 40.75 mg of C17H23NO · C4H6O6. USP Levonorgestrel RS

. Levorphanol Tartrate Injection

. Levorphanol Tartrate » Levorphanol Tartrate Injection is a sterile solu- tion of Levorphanol Tartrate in Water for Injec- tion. It contains not less than 93.0 percent and not more than 107.0 percent of the labeled amount of C17H23NO.C4H6O6 · 2H2O. Packaging and storage—Preserve in single-dose or in C17H23NO · C4H6O6 · 2H2O 443.49 multiple-dose containers, preferably of Type I glass. Morphinan-3-ol, 17-methyl-, [R-(R*,R*)]-2,3-dihydroxy- USP Reference standards 〈11〉— butanedioate (1:1) (salt), dihydrate. USP Endotoxin RS 17-Methylmorphinan-3-ol, tartrate (1:1) (salt) dihydrate Identification— [5985-38-6]. Anhydrous 407.47 [125-72-4]. A: To 1 mL of Injection add 1 drop of 3 N hydrochloric acid and 2 drops of ferric chloride TS. Heat to boiling, and » Levorphanol Tartrate contains not less than add 1 mL of potassium ferricyanide solution (1 in 200): a 99.0 percent and not more than 101.0 percent of blue-green color develops. B: The angular rotation of the Injection is levorotatory C17H23NO · C4H6O6, calculated on the anhydrous basis. (see Optical Rotation 〈781〉). Bacterial endotoxins 〈85〉—It contains not more than Packaging and storage—Preserve in well-closed contain- 125.0 USP Endotoxin Units per mg of levorphanol tartrate. ers. Store at 25°, excursions permitted between 15° and pH 〈791〉: between 4.1 and 4.5. 30°. Other requirements—It meets the requirements under In- USP Reference standards 〈11〉— jections 〈1〉. USP Levorphanol Tartrate RS USP 36 Official Monographs / Levothyroxine 4105

Assay—Transfer an accurately measured volume of Injec- of USP Levorphanol Tartrate RS in the same medium having tion, equivalent to about 40 mg of levorphanol tartrate, to a a known concentration of about 80 µg of anhydrous 125-mL separator. Add 5 g of sodium chloride and sufficient levorphanol tartrate per mL, in 1-cm cells at the wavelength sodium bicarbonate to render the solution alkaline to litmus, of maximum absorbance at about 279 nm, with a suitable add an additional 100 mg of sodium bicarbonate, and ex- spectrophotometer, using 0.1 N hydrochloric acid as the tract the levorphanol with five 20-mL portions of a mixture blank. Calculate the quantity, in mg, of C17H23NO · C4H6O6 · of 3 volumes of ether and 1 volume of chloroform. Pass the 2H2O in the Tablet taken by the formula: combined extracts through a layer of about 10 g of granular anhydrous sodium sulfate into a 500-mL conical flask, and (443.49 / 407.47)(TC / D)(AU / AS) evaporate to a volume of about 30 mL. Add about 50 mL of chloroform and 1 drop of methanolic methyl red TS, and in which 443.49 and 407.47 are the molecular weights of titrate with 0.01 N perchloric acid in dioxane VS to a red the hydrated and anhydrous forms of levorphanol tartrate, endpoint. Perform a blank determination, and make any respectively; T is the labeled quantity, in mg, of levorphanol necessary correction. Each mL of 0.01 N perchloric acid is tartrate in the Tablet; C is the concentration, in µg per mL, equivalent to 4.435 mg of C17H23NO · C4H6O6 · 2H2O. of USP Levorphanol Tartrate RS, on the anhydrous basis, in the Standard solution; D is the concentration, in µg per mL, of levorphanol tartrate in the solution from the Tablet, based on the labeled quantity per Tablet and the extent of dilution; and AU and AS are the absorbances of the solution

. Levorphanol Tartrate Tablets from the Tablet and the Standard solution, respectively. Assay—Weigh and finely powder not less than 20 Tablets. Weigh accurately a portion of the powder, equivalent to » Levorphanol Tartrate Tablets contain not less about 40 mg of levorphanol tartrate, transfer to a 125-mL than 93.0 percent and not more than 107.0 per- separator, add 20 mL of water and sufficient sodium bicar- cent of the labeled amount of levorphanol tar- bonate to render the suspension alkaline to litmus, and pro- trate (C17H23NO · C4H6O6 · 2H2O). ceed as directed in the Assay under Levorphanol Tartrate In- jection, beginning with “add an additional 100 mg of Packaging and storage—Preserve in well-closed contain- sodium bicarbonate.” ers. USP Reference standards 〈11〉— USP Levorphanol Tartrate RS

. Identification— Levothyroxine Sodium A: Powder finely a number of Tablets. To a portion of the powder, equivalent to about 1 mg of levorphanol tartrate, add 1 mL of water, 1 drop of 3 N hydrochloric acid, and 2 drops of ferric chloride TS, and heat to boiling. To the hot solution add 1 mL of potassium ferricyanide solution (1 in 200): a bluish color develops. B: Powder a number of Tablets, equivalent to about

60 mg of levorphanol tartrate, and transfer the mixture to a C15H10I4NNaO4 · xH2O (anhydrous) 798.85 small separator. Add 10 mL of water, dissolve as much of L-Tyrosine, O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-, the powder as possible, add about 400 mg of sodium bicar- monosodium salt, hydrate; bonate, and extract with a 50-mL portion of chloroform. Monosodium L-thyroxine hydrate [25416-65-3]. Evaporate the filtered chloroform extract on a steam bath to Anhydrous [55-03-8]. a small volume, dilute with chloroform to 10 mL, and deter- mine the angular rotation: the solution is levorotatory (see DEFINITION Optical Rotation 〈781〉). Levothyroxine Sodium is the sodium salt of L-3,3′,5,5′-te- Dissolution 〈711〉— traiodothyronine. It contains NLT 97.0% and NMT Medium: water; 500 mL. 103.0% of levothyroxine sodium (C15H10I4NNaO4), calcu- lated on the anhydrous basis. Apparatus 2: 50 rpm. Time: 30 minutes. IDENTIFICATION

Procedure—Determine the amount of C17H23NO · C4H6O6 · 2H2O dissolved from UV absorbances at the wavelength of Change to read: maximum absorbance at about 279 nm on filtered portions of the solution under test, suitably diluted with water, in • A. ▲INFRARED ABSORPTION 〈197〉: [NOTE—Methods de- comparison with a Standard solution having a known con- scribed in Infrared Absorption 〈197K〉 or 〈197A〉 may be centration of USP Levorphanol Tartrate RS in the same me- used.]▲USP36 dium. Tolerances—Not less than 75% (Q) of the labeled amount Delete the following: of C17H23NO · C4H6O6 · 2H2O is dissolved in 30 minutes.

Uniformity of dosage units 〈905〉: meet the require- ▲ ments. • B. Acid sodium chloride solution: Alcohol, 1 N sodium hy- Procedure for content uniformity—Transfer 1 Tablet to a droxide, hydrochloric acid, and water (25:10:10:30) glass-stoppered flask, add 25.0 mL of 0.1 N hydrochloric Sample: 0.5 mg acid, and allow the Tablet to disintegrate. Shake well, and Analysis: Add 7.5 mL of Acid sodium chloride solution and filter through a small filter paper, discarding the first portion 1 mL of 10 mg/mL sodium nitrite solution to the Sam- of the filtrate. Dilute a portion of the filtrate quantitatively ple. Allow to stand in the dark for 20 min, and add and stepwise, if necessary, to provide a solution containing 1.25 mL of ammonium hydroxide. about 80 µg of levorphanol tartrate per mL. Concomitantly determine the absorbances of this solution and of a solution