Health & Environmental Research Online (HERO)


Print Feedback Export to File
1625244 
Journal Article 
HPLC AND NMR METHODS FOR THE QUANTITATION OF THE (R)-ENANTIOMER IN (-)-(S)-TIMOLOL MALEATE DRUG RAW-MATERIALS 
Lacroix, PM; Dawson, BA; Sears, RW; Black, DB 
1994 
Yes 
Chirality
ISSN: 0899-0042 
6 
6 
484-491 
English 
WOS:A1994PJ55200006 
HPLC and H-1-NMR methods for the quantitation of the (R) enantiomer in (-)-(S)-timolol maleate were developed and validated. The HPLC method requires a 25
cm x 4.6 mm 5 mu m Chiracel OD-H (cellulose tris-3, 5-dimethylphenylcarbamate) column, a mobile
phase of 0.2% (v/v) diethylamine and 4% (v/v) isopropanol in hexane at a flow rate of 1 ml/min
and UV detection at 297 nm. A system suitability test was devised to verify the separation of the
(R)- and (S)-enantiomers of timolol from other drug-related impurities. The NMR method requires
the use of a high-held NMR spectrometer (>360 MHz) and a chiral solvating agent, (-)-(R)-2,2,2-
trifluoro-1-(9-anthrylethanol) (R-TFAE). The limits of quantitation were 0.05% and 0.2% (m/m) for
HPLC and NMR, respectively. The methods were applied to the determination of the (R)-enantiomer
in eight lots of raw material. The results for the two methods were in very goad agreement, with
results ranging from 0.1 to 4.1% (m/m) by HPLC and none detected to 4.3% (m/m) by NMR. The USP
method for specific rotation was found to be unsuitable for detecting the presence of low levels
of the (R)enantiomer in (-)-(S)-timolol maleate. Published 1994 Wiley-Liss, Inc. 
TIMOLOL MALEATE; QUANTITATION OF ENANTIOMERS BY HPLC; QUANTITATION OF ENANTIOMERS BY NMR; OPTICAL PURITY; CHIRAL SEPARATION; CELLULOSE TRIS-3,5-DIMETHYLPHENYLCARBAMATE (CHIRACEL OD-H); CHIRAL SOLVATING AGENTS