2761
Supplement II,JP XVI Official Monographs Add the following:
Telmisartan
テルミサルタン
C 33H 30N 4O 2:514.624?-s [4-Methyl-6-(1-methyl-1H -benzimidazol-2-yl)–2-propyl-1H -benzimidazol-1-yl]methyl t biphenyl-2-carboxylic acid [144701-48-4]
Telmisartan,when dried,contains not less than 99.0z and not more than 101.0z of C 33H 30N 4O 2.
黄豆的英文Description Telmisartan occurs as a white to pale yellow crystalline powder.
It is freely soluble in formic acid,slightly soluble in methanol,very slightly soluble in ethanol (99.5),and practi-cally insoluble in water.
It shows crystal polymorphism.Identification (1)Determine the absorption spectrum of a solution of Telmisartan in methanol (7in 1,000,000)as directed under Ultraviolet-visible Spectrophotometry <2.24>,and compare the spectrum with the Reference Spectrum:both spectra exhibit similar intensities of absorption at the same wavelengths.
(2)Determine the infrared absorption spectrum of Tel-misartan as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>,and compare the spectrum with the Reference Spectrum:both spectra exhibit similar intensities of absorption at the same wave numbers.If any difference appears between the spectra,dissolve Tel-misartan in ethanol (95)by warming,and cool in ice.Collect the crystals formed,dry,and perform the test with the crys-tals.
Purity (1)Heavy metals <1.07>—Proceed with 2.0g of Telmisartan according to Method 2,and perform the test.Prepare the control solution with 2.0mL of Standard Lead solution (not more than 10ppm).
(2)Related substances—To 25mg of Telmisartan add 5mL of methanol and 0.1mL of sodium hydroxide TS,and dissolve with the aid of ultrasonic waves.To this solution add methanol to make 10mL,and u this solution as the sample solution.Pipet 1mL of the sample solution,add methanol to make exactly 100mL,and u this solution as the standard solution.Perform the test with exactly 2m L each of the sample solution and standard solution as direct-ed under Liquid Chromatography <2.01>according to the
following conditions,and determine each peak area by the automatic integration method:the area of the peak,having the relative retention time of about 1.7to telmisartan,ob-tained from the sample solution is not larger than 1/5times the peak area of telmisartan obtained from the standard so-lution,the area of the peak other than telmisartan and the above mentioned peak from the sample solution is not larger than 1/10times the peak area of telmisartan from the stan-dard solution,and the total area of the peaks other than tel-misartan from the sample solution is not larger than the peak area of telmisartan from the standard solution.For this calculation u the area of the peak,having th
e retention time of about 0.7to telmisartan,after multiplying by its rel-ative respon factor 1.2.Operating conditions —
Detector:An ultraviolet absorption photometer (wave-length:230nm).
Column:A stainless steel column 4.0mm in inside di-ameter and 12.5cm in length,packed with octadecyl-silanized silica gel for liquid chromatography (5m m in parti-cle diameter).
Column temperature:A constant temperature of about 409C.
公司乔迁Mobile pha A:Dissolve 2.0g of potassium dihydrogen phosphate and 3.4g of sodium 1-pentanesulfonate in 1000mL of water,and adjust to pH 3.0with diluted phosphoric acid (1in 10).
厉害日文Mobile pha B:A mixture of acetonitrile and methanol (4:1).
Flowing of the mobile pha:Control the gradient by mix-ing the mobile phas A and B as directed in the following table.
Time after injection of sample (min)
Mobile pha A
(vol z )
Mobile pha B
(vol z )
0–25
tinami70ª20
30ª80
apus秋瓷炫主演的电视剧Flow rate:1.0mL per minute.
Time span of measurement:About 2times as long as the retention time of telmisartan,beginning after the solvent peak.
System suitability —
Test for required detectability:Pipet 5mL of the standard solution,add methanol to make exactly 100mL.Confirm that the peak area of telmisartan obtained with 2m L of this solution is equivalent to 3.
5to 6.5z of that obtained with 2m L of the standard solution.
System performance:When the procedure is run with 2m L of the standard solution under the above operating condi-tions,the number of theoretical plates and the symmetry factor of the peak of telmisartan are not less than 45,000and not more than 1.2,respectively.
System repeatability:When the test is repeated 6times with 2m L of the standard solution under the above operat-ing conditions,the relative standard deviation of the peak area of telmisartan is not more than 5z .
(3)Residual solvent—Being specified parately when
2762Supplement II,JP XVI Official Monographs
the drug is granted approval bad on the Pharmaceutical Affairs Law.
Loss on drying<2.41>Not more than0.5z(1g,1059C,4 hours).
no offenResidue on ignition<2.44>Not more than0.1z(1g).
Assay Weigh accurately about0.19g of Telmisartan, previously dried,dissolve in5mL of formic acid,add75mL of acetic anhydride,and titrate<2.50>with0.1mol/L per-chloric acid VS(potentiometric titration).Perform a blank determination in the same manner,and make any necessary correction.
Each mL of0.1mol/L perchloric acid VS
kaku
＝25.73mg of C33H30N4O2
Containers and storage Containers—Tight containers.
Add the following:
Telmisartan Tablets
テルミサルタン錠
Telmisartan Tablets contain not less than95.0z and not more than105.0z of the labeled amount of telmisartan(C33H30N4O2:514.62).
Method of preparation Prepare as directed under Tablets, with Telmisartan.
Identification Powder Telmisartan Tablets.To a portion of the powder,equivalent to0.7mg of Telmisartan,add100 mL of methanol,shake well,and filter through a membrane filter with a pore size not exceeding0.45m m.Determine the absorption spectrum of the filtrate as directed under Ultrav-iolet-visible Spectrophotometry<2.24>:it exhibits maxima between226nm and230nm and between295nm and299 nm.
Uniformity of dosage units<6.02>Perform the test accord-ing to the following method:it meets the requirement of the Content uniformity test.
To1tablet of Telmisartan Tablets add4V/5mL of a mix-ture of water and methanol(1:1),disintegrate the tablet us-ing ultrasonic waves,and add a mixture of water and methanol(1:1)to make exactly V mL so that each mL con-tains about0.8mg of telmisartan(C33H30N4O2).Filter this solution through a membrane filter with a pore size not exceeding0.45m m,discard10mL of the first filtrate,pipet5 mL of the subquent filtrate,add a mixture of water and methanol(1:1)to make exactly50mL,and u this solution as the sample solution.Then,proceed as directed in the Assay.
Amount(mg)of telmisartan(C33H30N4O2)
＝M S×A T/A S×V/25
M S:Amount(mg)of telmisartan for assay Dissolution<6.10>When the test is performed at50revolu-tions per minute according to the Paddle method,using900 mL of2nd fluid for dissolution test as the dissolution medi-um,the dissolution rate in30minutes of Telmisartan Tablets is not less than85z.
Start the test with1tablet of Telmisartan Tablets, withdraw not less than20mL of the medium at the specified minute after starting the test,and filter through a membrane filter with a pore size not exceeding0.45m m.Discard not less than5mL of the first filtrate,pipet V mL of the subquent filtrate,add the dissolution medium to make exactly V?mL so that each mL contains about11m g of telmisartan (C33H30N4O2),and u this solution as the sample solution. Separately,weigh accurately about22mg of telmisartan for assay,previously dried at1059C for4hours,add10mL of a solution of meglumine in methanol(1in500),dissolve with the aid of ultrasonic waves,and add methanol to make ex-actly50mL.Pipet5mL of this solution,add the dissolution medium to make exactly200mL,and u this solution as the standard solution.Determine the absorbances,A T and A S, at296nm of the sample solution and standard solution as directed under Ultraviolet-visible Spectrophotometry<2.24>, using the dissolution medium as the control.
Dissolution rate(z)with respect to the labeled amount of telmisartan(C33H30N4O2)
＝M S×A T/A S×V?/V×1/C×45
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M S:Amount(mg)of telmisartan for assay
C:Labeled amount(mg)of telmisartan(C33H30N4O2)in1 tablet
Assay Weigh accurately the mass of not less than20Tel-misartan Tablets,and powder.Weigh accurately a portion of the powder,equivalent to about80mg of telmisartan (C33H30N4O2),add80mL of a mixture of water and methanol(1:1),shake thoroughly,and add a mixture of water and methanol(1:1)to make exactly100mL.Filter this solution through a membrane filter with a pore size not ex-ceeding0.45m m.Discard the first10mL of the filtrate, pipet5mL of the subquent filtrate,add a mixture of water and methanol(1:1)to make exactly50mL,and u this solu-tion as the sample solution.Separately,weigh accurately about20mg of telmisartan for assay,previously dried at105 9C for4hours,add10mL of a solution of meglumine in a mixture of water and methanol(1:1)(1in500),dissolve by shaking well,and add a mixture of water and methanol(1:1) to make exactly25mL.Pipet5mL of this solution,add a mixture of water and methanol(1:1)to make exactly50mL, and u this solution as the standard solution.Perform the test with exactly10m L each of the sample solution and stan-dard solution as directed under Liquid Chromatography <2.01>according to the following conditions,and determine the peak areas,A T and A S,of telmisartan in each solution.
Amount(mg)of telmisartan(C33H30N4O2)
＝M S×A T/A S×4棒棒糖制作
M S:Amount(mg)of telmisartan for assay
