(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.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/22982 must be provided.

1. The comparison of the stability indicating  two HPLC methods and their application for the determination of bosentan in coated tablets 
2. Application of the new data processing method for photodiode array detector in the analysis of drug substances
3. Improved manufacturing process of bosentan monohydrate.
4. Development and validation of the GC method for quantitative determination of semi-volatile solvents in pharmaceutical substance Bosentan
5. Synthesis of potential impurities of loteprednol etabonate and methods for chemical purity determination
6. Assessment of selected synthesis of bosentan towards elimination of known impurities.
7. Investigation of unknown impurities in cyclic dermorphin analogue by HPLC-MS
8. Development and validation of the HPLC-UV method for impurities determination in duloxetine hydrochloride
9. Development and validation of HPLC method. Review of selected cases.
10. Preparation of protoaescigenin from escin.
11. Iontophoretic delivery of selected antiparkinsonian agents in vitro
12. Opimisation of preparation of TZ-6
13. HPLC method as an analitycal control of synthesis and determination of TZ-S
14. Validation of a HPLC method for LI-S analysis
15. HPLC Methods for Stress Testing of ZL-S Drug Substances
16. The evaluation of tolterodine tartrate synthesis based on patent EP 0 325 574 B1.
17. Disubstituted indolo[2,3-b]quinoline derivatives - the cytotoxic activity in vitro against various human tumor cell lines.
18. Mono substituted 5H- and 6H-indolo[2,3-b]quinoline derivatives and their ability to overcome the barrier of drug resistance.
19. Synthesis of selected ¹⁴C radiolabelled compounds in recent investigations of new analytical method applied in accelerated drug development (EUMAPP).
20. HPLC as a method for analytical control of synthesis and determination of tolterodine (TD-S)
21. Development of HPLC and GC methods for analysis of Zolmitriptan of pharmaceutical purity
22. QUINONES AND HYDROQUINONES SEPARATION AND DETERMINATION BY HPLC CHROMATOGRAPHY
23. MONO SUBSTITUTED 5H-INDOLO[2,3-B]- QUINOLINE DERIVATIVES AND THEIR ABILITY TO OVERCOME THE BARRIER OF DRUG RESISTANCE.
24. DISUBSTITUTED INDOLO[2,3-b]QUINOLINE DERIVATIVES. THE CYTOTOXIC ACTIVITY IN VITRO AGAINST VARIOUS HUMAN TUMOR CELL LINE.
25. NEW IMPROVED METHOD OF POLYMORPHIC α FORM OF IMATINIB MESYLATE (GLEEVEC^®) SYNTHESIS.