Stereoselective HPLC analysis of mexiletine enantiomers : pharmacokinetics and protein binding in humans

Content Provider	Semantic Scholar
Author	Igwemezie, Linus Nnamdi
Copyright Year	1986
Abstract	M e x i l e t i n e i s a r e l a t i v e l y new c l a s s IB a n t i a r r h y t h m i c a g e n t , s i m i l a r i n s t r u c t u r e and p h a r m a c o l o g i c a l e f f e c t s t o l i d o c a i n e . I t i s e f f e c t i v e m a i n l y a g a i n s t v e n t r i c u l a r a r r h y t h m i a s and can be a d m i n i s t e r e d by the o r a l r o u t e , m e x i l e t i ne i s a c h i r a l drug which i s used c l i n i c a l l y as the rac e m i c m i x t u r e . The ena n t i o m e r s of numerous c h i r a l drugs have been shown t o d i f f e r i n t h e i r d i s p o s i t i o n i n the body due t o t h e i r s t e r e o s e l e c t i v e pharmacodynamic and/or p h a r m a c o k i n e t i c p r o p e r t i e s . The r e l a t i v e a n t i a r r h y t h m i c p o t e n c i e s of the i n d i v i d u a l e n a n t i o m e r s of m e x i l e t i n e have n ot been s t u d i e d , nor have t h e i r p h a r m a c o k i n e t i c s been p r o p e r l y e l u c i d a t e d . Thus, the p r e s e n t s t u d y was aimed a t d e v e l o p i n g a h i g h l y s e n s i t i v e and s t e r e o s e l e c t i v e assay f o r m e x i l e t i n e e n a n t i o m e r s which w i l l be u t i l i z e d t o st u d y t h e i r p h a r m a c o k i n e t i c s and i n v i t r o serum p r o t e i n b i n d i n g . A h i g h p e r f o r m a n c e 1 i q u i d c h r o m a t o g r a p h i c assay was devel o p e d u s i n g the P i r k l e i o n i c c h i r a l s t a t i o n a r y phase. The ena n t i o m e r s were r e s o l v e d as t h e i r 2-naphthoyl d e r i v a t i v e s . The HPLC m o b i l e phase c o n s i s t e d of 5.5% 2-p r o p a n o l i n hexane and was d e l i v e r e d a t a f l o w r a t e o f 1.4 mL/min. D e t e c t i o n of the e n a n t i o m e r i c d e r i v a t i v e s was a c c o m p l i s h e d w i t h a f l u o r e s c e n c e d e t e c t o r [230 nm (Ex) and
File Format	PDF HTM / HTML
DOI	10.14288/1.0096727
Alternate Webpage(s)	https://open.library.ubc.ca/media/download/pdf/831/1.0096727/2
Alternate Webpage(s)	https://doi.org/10.14288/1.0096727
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article