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Investigation of unknown impurity of TD-S by HPLC-MS

Tomasz Giller ,  Maria Puchalska ,  Barbara Wolanin ,  Wojciech Łuniewski 

Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland


(R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-methylphenol (TD-S) is a potent anticholinergic agent used in treatment of urinary incontinence. In this work we show the technological process which leads to obtaining TD-S of pharmaceutical purity.

In Fig.1, the synthesis path of TD-S is presented. Straightforward application of this scheme in the laboratory scale led to obtaining of TD-S with a purity not meeting the requirements of the european regulatory authorities. In particular, the amount of an unidentified impurity (1) characterized by HPLC relative retention time 1,2 was exceeding the acceptable impurity thershold.

Attempts to purify the substance by means of crystallization were found unsuccessful. Thus, it appeared necessary to identify the potential source of impurity in the intermediate TD-5A. Investigations carried out by HPLC-MS-MS technique in both, the final product and the intermediate, allowed elucidating the potential structure of the impurity (1) and linking it to other structures found in the TD-5A intermediate.

Finally it was shown that purification of the intermediate from selected impurities allows obtaining the final product with the pharmaceutical purity.


Fig.1 Synthesis path of TD-S

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Submitted: 2010-03-15 09:07
Revised:   2010-04-07 13:30