1. STABILITY INDICATING HPLC METHODS FOR CYCLODEXTRIN DERIVATIVES 1 ChiroQuest Chiral Technologies Development Ltd., Budapest, Hungary 2 CycloLab Cyclodextrin R&D Laboratory Ltd., Budapest, Hungary, e-mail: szeman.j@cyclolab.hu 3 Semmelweis University, Faculty of Pharmacy, Department of Pharmaceutics, Hőgyes Endre u. 7, Budapest, H-1092, Hungary Gábor Varga 1, Krisztina Ludányi 3, Julianna Szemán 2, Imre Klebovich 3, Lajos Szente 2 The characterisation of the isomer distribution and purity of cyclodextrin (CD) derivatives, their routine quality control and examination of their stability during storage are still a real problem. Using even the most sophisticated analytical methods the separation and identification of all components is far beyond the possibility. CD-Screen column designed for cyclodextrin analysis contains susbstituted phenyl groups bonded to silicagel stationary phase. This stationary phase suitable for fingerprint characterization of different CD derivatives, as well as, gives the possibility to follow their degradation [1]. CDs and CD derivatives are relatively stable substances, only a few articles can be found on their decomposition [2.3,4]. However, to follow the hydrolytical, oxidative or enzymatic decomposition of CDs and their derivatives can be interesting not only as research subject, but also from practical point of view. In this work our aim was to develop stability indicating HPLC methods for CD derivatives, to follow their degradation pathways by studying the structures of the degradation products. INTRODUCTION RESULTS AND DISCUSSION Acidic decomposition of RAMEB CONCLUSIONS  The acidic degradation of CD derivatives resulted in substituted linear dextrins, which show the same complexity as the parent cyclodextrins  The first step of the acidic hydrolysis is the ring opening; the further fragmentation of the substituted maltoheptaoses is faster in case of HPBCD than in case of RAMEB  The obtained information provides the theoretical basis of the future development: development of a simple method using even RI or ELS detection for quantitation of the formed decomposition products of cyclodextrin derivatives [1] J. Szemán, K. Csabai, K. Kékesi, l. Szente, G. Varga; J. Chromatography A, 1116, 76-82 (2006) [2] S. Kawakishi, A. Satake, T. Komiya, M. Namiki; Starch/Stärke 25 203-206 (1983) [3] K. Uchida, S. Kawakishi; Agricult. Biol. Chem. 50(2) 54-57 (1986) [4] É. Fenyvesi, K. László; Cyclodextrin News 15(11) 203-206 (2001) REFERENCES The authors are grateful to Ms. Zs. Zachár and Ms. E. Erdei to their valuable technical assistance. The work was supplied by the National Research Fund (NKFP-1A-041/2004 and NKFP1-012/2005). ACKNOWLEDGEMENT Forced degradation of CDs Samples stored under stress conditions: 2-(hydroxy)propyl-  -cyclodextrin (HPBCD) Randomly methylated  -cyclodextrin (RAMEB) Decomposition under stress conditions: In 1 M hydrochloric acid solution  moderate decomposition In 1 M sodium hydroxide solution  no decomposition In 30% hydrogen peroxide solution  slight decomposition Linear, methylated maltoheptaoses MS detection ELSD detection Acidic decomposition of HPBCD Methylated maltooligomers RAMEB components DS: 8-16 DS: 12 DS: 15 DS: 9 HPBCD components DS: 1-10 Hydroxypropylated maltooligomers Linear, hydroxypropylated maltoheptaoses DS: 14 MS detection ELSD detection Extracted ion chromatogram