2172
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Pharmacol. 2005, 57, 1432–1843; (b) Muñoz, D.; Cantu, D.; Gonzalez, A.;
Meneses, A.; Mohar, A.; Astudillo-de la Vega, H.; Nguyen, B. J. Clin. Oncol. 2007,
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2. Lerchen, H.-G.; von dem Bruch, K.; Buamgarten, J.; Sperzel, M. U.S. Patent
6,492,335, 2002.
3. Sagiraju, S.; Jursic, B. S. Carbohydr. Res. 2008, 343, 1180–1190.
4. For instance, see: (a) Shimada, T.; Yamazaki, H.; Mimura, M.; Inui, Y.;
Guengerich, F. P. J. Pharmacol. Exp. Ther. 1994, 270, 414–423; (b) Guengerich,
F. P. Chem. Res. Toxicol. 1991, 4, 391–407.
adjusted for the molecular weight of a proton, ammonium, and so-
dium ion. That was perfectly demonstrated on the positive ESI
mass spectra of 3 in aqueous
c-CD (Fig. 9). Noticeable are signals
for -CD inclusion complex with two 3 at m/z 1136.0 and
c
c-CD
inclusion complex of partially hydrolyzed 3 at 882.9. All the other
signals correspond either to molecule 3 (signal at m/z 509.7), par-
tially hydrolyzed 3 (signal at m/z 487.6), fully hydrolyzed 3 (signal
at m/z 395.5) or their various molecular associates (Fig. 9).
5. For use of cyclodextrins for the drug delivery, see: Challa, R.; Ahuja, A.; Ali, J.;
Khar, R. K. AAPS PharmSciTech 2005, 6, E329.
6. Burkert, W. G.; Owensby, C. N.; Hinze, W. L. J. Liq. Chromatogr. 1981, 4, 1065–
1085.
7. Shigehiro Kamitori, S.; Toyama, Y.; Matsuzakam, O. Carbohydr. Res. 2001, 332,
235–240.
8. Kamigauchi, M.; Kawanishi, K.; Ohishi, H.; Ishida, T. Chem. Pharm. Bull. 2007, 55,
729–733.
9. For instance, see: Chan, L. W.; Kurup, T. R. R.; Muthaiah, A.; Thenmozhiyal, J. C.
Int. J. Pharm. 2000, 195, 71–79.
10. For instance, see: Wong, T. C., Micellar Systems: Nuclear Magnetic Resonance
Spectroscopy. In Somasundaran, P., Hubbardlopdia, A. (Eds.), Encyclopedia of
Surface and Colloid Science, 2nd ed.; CRC Press: Boca Raton, 2006, pp 3738–
3756.
11. For instance see: Beni, S.; Szakacs, Z.; Csernak, O.; Barcza, L.; Noszal, B. Eur. J.
Pharm. Sci. 2007, 30, 167–174.
12. Baer, A.; Macartney, D. H. Org. Biomol. Chem. 2005, 3, 1448–1453.
13. For instance see: Raji, M. A.; Frycak, P.; Beall, M.; Sakrout, M.; Ahn, J.-M.; Bao,
Y.; Armstrong, D. W.; Schug, K. A. Int. J. Mass Spectrom. 2007, 262, 232–240.
14. One can also speculate that these aggregates could be formed during ionization
in the MS source. For instance see: Stefansson, M.; Sjöberg, P. J.; Markides, K. E.
Anal. Chem. 1996, 68, 1792–1797.
4. Conclusions
Water-soluble A007 prodrug interactions with
b-cyclodextrin, and -cyclodextrin were studied with ESI mass
a-cyclodextrin,
c
spectrometry. Cyclodextrins were used for several purposes; to
solubilize the prodrug, change the stability of the prodrug; and
as a prodrug carrier. It was demonstrated that in an aqueous cyclo-
dextrin solution, the half-life of prodrug 3 decreased to ꢀ4–5 h,
which is ideal for in vivo drug release. It was also demonstrated
that during prodrug hydrolysis, various molecular aggregates were
formed that can substantially alter the drug’s absorption and re-
lease capability.14 Therefore, cyclodextrin seems to be crucial for
both drug delivery capability and drug release control through
altering the prodrug half-life in blood plasma.
15. For general information about ESIMS sample preparation see: Li, S.; Jia, J.; Liu,
G.; Wang, W.; Cai, Y.; Wang, Y.; Yu, C. J. Chromatogr., B 2008, 870, 63–67. and
references cited therein.
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