Lapas attēli
PDF
ePub
[merged small][merged small][merged small][merged small][ocr errors][merged small][merged small]

C

Clarithromycin activity in the clarithromycin working standard solution in milligrams per milliliter; and d = Dilution factor of sample filtrate.

(14) Azithromycin. Proceed as directed in § 452.60(b)(1) of this chapter, except:

(1) Dissolution medium. Dissolve 85.2 grams of sodium phosphate dibasic and dilute to volume with ultrapure deionized or high-performance liquid chromatographic-grade water in a stoppered 2-liter graduated cylinder. Dilute this entire solution in an appropriate, suitably sized container with 4 liters of ultrapure deionized or highperformance liquid chromatographicgrade water. Adjust the pH to 6.0±0.05 with concentrated hydrochloric acid (about 40.5 milliliters). Add 600 milligrams of trypsin and mix well.

(ii) Preparation of the standard and sample solutions—(a) Standard solution. Accurately weigh approximately 15 milligrams of the azithromycin working standard into a 50-milliliter volumetric flask. Add 25 milliliters of the dissolution medium and sonicate briefly. Dilute to volume with dissolution medium and mix well. Pipet 2.0 milliliters of this solution into a 25-milliliter volumetric flask and dilute to volume with the mobile phase described in § 452.60(b)(1)(1) of this chapter. Pipet 4.0 milliliters of this solution into a 25milliliter volumetric flask and bring to volume with the mobile phase.

(b) Sample solution. Filter the sample solutions through a 0.45-micron filter before use. Pipet 2.0 milliliters of the filtered aliquot into a 25-milliliter volumetric flask and dilute to volume with the mobile phase described in § 452.60(b)(1)(1) of this chapter. Pipet 4.0 milliliters of this solution into another 25-milliliter volumetric flask and bring to volume with the mobile phase. The solution is stable at room temperature for 24 hours.

(c) Calculations. Determine the percent of azithromycin dissolved as follows:

Percent azithromycin_ A, XP,×DƑ×100

where:

dissolved

=

F

A,XW

[blocks in formation]

If more than 15 milliliters of dissolution medium are removed, correct for the volume removed; and

Wu Theoretical azithromycin content (mg) of capsule.

(15) Cefprozil. Proceed as directed in § 442.80(b)(1) of this chapter except:

(i) Sample solutions. Filter the sample solutions through a 0.45-micron filter before use. Use the sample solution as it is removed from the dissolution vessel without further dilution for the 250milligram tablet; prepare the sample solution for the 500-milligram tablet by diluting a 5-milliliter aliquot of the filtered solution to volume in a 10-milliliter volumetric flask with distilled water.

(ii) Calculations. Determine the total percent of cefprozil dissolved as follows:

Total percentage (mg cefprozil (Z) dissolved + mg cefprozil (E) dissolved)

[blocks in formation]
[blocks in formation]

As

с

Area of the cefprozil (Z) or cefprozil (E) response in the chromatogram of the cefprozil (Z) or cefprozil (E) standard;

= Concentration of the cefprozil (Z) or cefprozil (E) working standard solution in milligrams per milliliter; and

d = Dilution factor of the sample filtrate.

(16) Loracarbef—(i) Preparation of the working standard solution. Accurately weigh approximately 110 milligrams of the loracarbef working standard into a suitable-sized volumetric flask. Dissolve and dilute to volume with water. Further dilute an accurately measured portion with distilled water to obtain a known concentration of 0.02 milligram of loracarbef activity per milliliter.

(ii) Preparation of sample solutions. Dilute an accurately measured portion of the sample with sufficient distilled water to obtain a concentration of 0.02 milligram of loracarbef activity per milliliter (estimated).

(iii) Procedure. Using a suitable spectrophotometer and water as the blank, determine the absorbance of each standard and sample solution at the absorbance maximum at approximately 260 nanometers. Determine the exact position of the absorbance maximum for the particular instrument used.

(iv) Calculations. Determine the total amount of loracarbef dissolved as follows:

[blocks in formation]

c = Concentration of the working standard solution in milligrams per milliliter; and d = Dilution factor of the sample filtrate.

(17) Cefadroxil hemihydrate. Proceed as directed in paragraph (c)(1) of this section, except use the cefadroxil working standard and measure the absorbance at the absorption peak of approximately 264 nanometers.

(18) Rifabutin—(i) Preparation of the working standard solution. Accurately weigh approximately 45 milligrams of the rifabutin working standard into a suitable-sized volumetric flask. Dissolve and dilute to volume with 0.01N hydrochloric acid (prepared by diluting 5.0 milliliters of hydrochloric acid (37 percent) to 6 liters with distilled water) to obtain a concentration of approximately 13 micrograms rifabutin activity per milliliter.

(ii) Preparation of sample solutions. Forty-five minutes after the beginning of the rotation, withdraw a 10-milliliter aliquot from the vessel. Dilute a 2-milliliter portion of the sample to 25 milliliters with 0.01N hydrochloric acid.

(iii) Procedure. Using a suitable spectrophotometer and 0.01N hydrochloric acid as the blank, determine the absorbance of each standard and sample solution at the absorbance maximum at approximately 280 nanometers. Determine the exact position of the absorbance maximum for the particular instrument used.

(iv) Calculations. Determine the total amount of rifabutin dissolved as follows:

[blocks in formation]

(19) Cefpodoxime proxetil—(1) Dissolution fluid: 0.04 molar glycine buffer, pH 3.0 (A) Stock solution. Dissolve 54.5 grams of glycine (aminoacetic acid) and 42.6 grams of sodium chloride in about 500 milliliters of deionized water in a 1-liter volumetric flask. Add cautiously, and with swirling, 14.2 milliliters of concentrated hydrochloric acid. Cool to room temperature. Dilute to volume with deionized water and mix. Check the pH of the solution obtained by diluting 50 milliliters of the stock solution to 900 milliliters with deionized water. The pH should be 3.0±0.1. If necessary, adjust the pH of the stock solution with 50 percent sodium hydroxide or concentrated hydrochloric acid. Recheck that the pH of the working solution is 3.0±0.1.

(B) Working solution. Dilute 50 milliliters of stock solution to 900 milliliters with deionized water.

(ii) Preparation of the working standard solutions. Accurately weigh approximately 28 milligrams for the 100milligram tablets and 56 milligrams for the 200-milligram tablets of the cefpodoxime proxetil working standard and dissolve in 10 milliliters of methanol. Dilute to 200 milliliters with dissolution fluid. Prepare fresh daily.

(iii) Sample solutions. Filter the sample solutions through a 0.45-micron filter before use. Use the sample solution as it is removed from the dissolution vessel without further dilution.

(iv) Procedure. Using a suitable spectrophotometer and water as the blank, determine the absorbance of each standard and sample solution at the absorbance peak at approximately 259 nanometers. Determine the exact position of the absorption peak for the particular instrument used.

(v) Calculations. Determine the percent of label dissolved as follows:

Percent dissolved = (Asam Asid) X (C/L) X V X PX F1

[blocks in formation]
[blocks in formation]

(a) Equipment. A suitable high-performance liquid chromatograph equipped with:

(1) A suitable detection system specified in the monograph for the drug being tested;

(2) A suitable recording device of at least 25-centimeter deflection;

(3) A suitable chromatographic data managing system; and

(4) An analytical column, 3 to 30 centimeters long, packed with a material as defined in the monograph for the drug being tested; and if specified in that monograph, the inlet of this column may be connected to a guard column, 3 to 5 centimeters in length, packed with the same material of 40 to 60 micrometers particle size.

(b) Procedure. Perform the assay and calculate the drug content using the temperature, instrumental conditions, flow rate, and calculations specified in the monograph for the drug being tested. Use a detector sensitivity setting that gives a peak height for the working standard solution that is at least 50 percent of scale with typical chart speed of not less than 2.5 millimeters per minute. Use the equipment described in paragraph (a) of this section. Use the reagents, working standard solution, and sample solution described in the monograph for the drug being tested. Equilibrate and condition the column by passage of 10 to 15 void volumes of mobile phase followed by five replicate injections of the same volume of the working standard solution. Allow an operating time sufficiently long to obtain satisfactory separation and elution of the expected components after each injection. Record the peak responses and calculate the prescribed

system suitability requirements described for the system suitability test in paragraph (c) of this section.

(c) System suitability test. Select the system suitability requirements specified in the monograph for the drug being tested. Then, using the equipment and procedure described in this section, test the chromatographic system for assay as follows:

(1) Trailing factor or asymmetry factor. Calculate either the trailing factor (T), from distances measured along the horizontal line at 5 percent of the peak height above the baseline or the asymmetry factor (A,) measured at a point 10 percent of the peak height from the baseline; whichever is required in the appropriate monograph, as follows:

[blocks in formation]
[merged small][merged small][ocr errors][subsumed][merged small][ocr errors][subsumed][merged small][merged small][merged small][merged small][merged small][merged small][merged small][merged small][merged small][merged small][merged small]

TR n = 5.545 Wh

[merged small][ocr errors]
[blocks in formation]

t, Retention time of solute; and

tm=Retention time of solvent or unretained substance, calculated as follows:

[blocks in formation]
[blocks in formation]

where:

D-Column diameter in centimeters;

L=Column length in centimeters;

0.75-Average total column porosity; and F=Flow rate in milliliters per minute.

[51 FR 11572, Apr. 4, 1986, as amended at 54 FR 47351, Nov. 14, 1989]

§ 436.217 Film-coat rupture test.

(a) Immersion fluid. Dilute 6.0 milliliters of hydrochloric acid to 1,000 milliliters with water. During the performance of the test maintain the immersion fluid at a temperature of 37±0.5 °C by using a thermostatically controlled water bath.

(b) Immersion vessel. Use a suitable vessel, such as a 1-liter beaker.

(c) Operation. Add 750 milliliters of immersion fluid to the immersion vessel.

(d) Procedure. Drop a tablet into the immersion fluid and record the time for the tablet coat to rupture. Repeat the test with a further 19 tablets, testing not more than 10 tablets with a given volume of immersion fluid.

(e) Evaluation. The tablets pass the film-coat rupture test if the mean coat rupture time does not exceed 20 seconds and not more than 2 tablets have a coat rupture time exceeding 40 seconds.

[52 FR 42432, Nov. 5, 1987]

[blocks in formation]

(a) Equipment. Polarimeter capable of measuring optical rotatory activity at 365 nanometers: Perkin-Elmer Model 141 or equivalent, with a suitable 1-decimeter polarimeter tube.

(b) Reagents—(1) 4-methyl-2-pentanone. Meets ACS specifications.

(2) Phosphate-citrate buffer. Dissolve 61.0 grams of anhydrous disodium phosphate and 11.0 grams of citric acid in 950 milliliters of distilled water. Adjust the pH to 6.0 with 6N hydrochloric acid. Dilute to 1,000 milliliters with distilled water.

(c) Preparation of carbenicillin indanyl sodium sample and working standard solutions. Accurately weigh approximately 125 milligrams of the carbenicillin indanyl sodium sample or working standard into a 25-milliliter volumetric flask. Dissolve and dilute to volume with distilled water. Transfer a 5-milliliter aliquot to a 50-milliliter glass-stoppered centrifuge tube. Add 15 milliliters of the phosphate-citrate buffer and 20 milliliters of 4-methyl-2-pentanone; stopper and shake the tube for 10 seconds. Centrifuge at 2,000 revolutions per minute for 10 minutes to separate the phases. Remove about 15 milliliters of the upper (4-methyl-2pentanone solvent) phase and proceed as directed in paragraph (e) of this section.

cen

(d) Preparation of the blank. Place a 5milliliter aliquot of distilled water into a 50-milliliter glass-stoppered trifuge tube, add 15 milliliters of phosphate-citrate buffer and 20 milliliters of 4-methyl-2-pentanone; stopper and shake the tube for 10 seconds. Centrifuge at 2,000 revolutions per minute for 10 minutes to separate the phases. Remove about 15 milliliters of the upper phase and proceed as directed in paragraph (e) of this section.

(e) Procedure. Fill the polarimeter tube with the blank solution prepared as described in paragraph (d) of this section. Place the tube in the polarimeter. Adjust the polarimeter to zero rotation using a light source with a wavelength of 365 nanometers. Use the same procedure to determine the optical rotation of both the sample solution and the working standard solution prepared as directed in paragraph (c) of this section.

(f) Calculations. Calculate the carbenicillin content (potency) of the sample on an anhydrous basis as follows:

Micrograms of carbenicillin per

milligram of sample

Degrees of rotation of sample solution weight of working standard x100x micrograms of carbenicillin in each milligram of the working standard

Degrees of rotation of working standard solution ×
weight of sample × (100 – m)

« iepriekšējāTurpināt »