Timolol Maleate
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2-Propanol,1-(1,1-dimethylethyl)amino-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-,(S)-,(Z)-2-butenedioate (1:1)(salt).
(-)-1-(tert-Butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy]-2-propanol maleate (1:1)(salt) [26921-17-5].
»Timolol Maleate contains not less than 98.0percent and not more than 101.0percent of C13H24N4O3S·C4H4O4,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
A:
Infrared Absorption á197Mñ.
B:
Ultraviolet Absorption á197Uñ—
Solution:
25µg per mL.
Medium:
0.12Nhydrochloric acid.
Absorptivities at 294nm,calculated on the dried basis,do not differ by more than 3.0%.
Specific rotation á781Sñ:
between -11.7
and -12.5(l=405nm).
and -12.5(l=405nm).
Test solution:
50mg per mL,in 1.0Nhydrochloric acid.
pHá791ñ:
between 3.8and 4.3,in a solution containing 20mg per mL.
Loss on drying á731ñ—
Dry it in vacuum at 100to constant weight:it loses not more than 0.5%of its weight.
to constant weight:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.1%.
Heavy metals,Method IIá231ñ:
0.002%.
Chromatographic purity—
Dissolve 500mg in methanol to obtain 10.0mLof test solution.Dissolve an accurately weighed quantity of USP Timolol Maleate RSin methanol,and dilute quantitatively and stepwise with methanol to obtain Standard solutions having the following compositions:
| Standard solution |
Concentration (µg RS per mL) |
Percentage (%, for comparison with test specimen) |
| A | 200 | 0.4 |
| B | 100 | 0.2 |
| C | 50 | 0.1 |
Separately apply 10-µLportions of the solutions 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 chromatogram in a solvent system consisting of a mixture of chloroform,methanol,and ammonium hydroxide (80:20:1)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.Expose the plate to iodine vapors for 2hours,and locate the spots on the plate by examination under short-wavelength UVlight.Compare the intensities of any secondary spots observed in the chromatogram of the test solution,excluding the origin spot due to the maleate anion,with those of the principal spots in the chromatograms of the Standard solutions:no secondary spot is more intense than the principal spot obtained from Standard solution A(0.4%),and the sum of the intensities of all secondary spots,excluding any having intensities less than the principal spot obtained from Standard solution C,does not exceed 1.0%.
Organic volatile impurities,Method Iá467ñ:
meets the requirements.
Assay—
Dissolve about 800mg of Timolol Maleate,accurately weighed,in about 90mLof glacial acetic acid,and titrate with 0.1Nperchloric acid VS,determining the endpoint potentiometrically,using a platinum electrode and a sleeve-type calomel electrode containing 0.1Nlithium perchlorate in acetic anhydride (see Titrimetry á541ñ).Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 43.25mg of C13H24N4O3S·C4H4O4.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1933
Phone Number:1-301-816-8305