Nano Quantity Analyte Detector

W elc o m e

Welcome

NANO QUANTITY ANALYTE DETECTOR

A NEW AEROSOL BASED DETECTOR FOR HPLC

PRESENTED BY:P.SRI RAMA RAOM PHARM II YEAR

C O N T E N T S : -

B A C K G R O U N D & H I S T O R Y I N T R O D U C T I O N

O P E R A T I N G R E Q U R I M E N T S

W C P C O U N T E R P R I N C I P L E O F W C P C O U N T E R ` F U N C T I O N I N G O F N Q A D W H A T M A K E S N Q A D B E T T E R A D V A N T A G E S O F N Q A D U S E S O F N Q A D C O N C L U T I O N R E F E R E N C E S

N a n o Q u a n t i t y A n a l y t e D e t e c t o r A N E W A E R O S O L B A S E D D E T E C T O R F O R H P L C

B A C K G R O U N D & H I S T O R Y: - Tr a d i t i o n a l l y, H P L C s y s t e m s h a v e u s e d a U V

a b s o r b a n c e t e c h n i q u e t o d e t e c t c h e m i c a l c o m p o u n d s . B u t U V d e t e c t o r s a r e l i m i t e d t o a n a l y t e s t h a t c o n t a i n a c h r o m o p h o r e . A e r o s o l - b a s e d H P L C d e t e c t o r s o ff e r a n a d v a n t a g e b e c a u s e t h e y c a n b e u s e d w i t h a n y a n a l y t e t h a t i s l e s s v o l a t i l e t h a n t h e m o b i l e p h a s e , w i t h o r w i t h o u t a c h r o m o p h o r e .

T h e N Q A D o p e r a t i o n i s p a r t l y b a s e d o n o r g i n a l t e c h n i q u e s f r o m e a r l y w o r k o n c o n d e n s a t i o n n u c l e a t i o n l i g h t s c a t t e r i n g d e t e c t o r b y D r. Ko r o p c h a k & c o l l e a g u e s .

E a r l i e r a e r o s o l - b a s e d d e t e c t o r s , s u c h a s e v a p o r a t i v e l i g h t s c a t t e r i n g , h a v e l o w s e n s i t i v i t y d u e t o t h e l o w l i g h t s c a t t e r i n g l e v e l s o f s m a l l p a r t i c l e s a n d p h o t o d e t e c t o r d r i f t . D e t e c t o r s b a s e d o n t h e m e a s u r e m e n t o f c h a r g e d a e r o s o l a r e l i m i t e d b y i n e ffi c i e n t c h a r g i n g o f s m a l l p a r t i c l e s a n d e l e c t r o m e t e r n o i s e .


I N T R O D U C T I O N : -

A n e w, u n i v e r s a l H P L C d e t e c t o r t h e N Q A D ( N a n o Q u a n t i t y A n a l y t e D e t e c t o r ) . I t i s a n e w a n d c o m p l e t e l y d i ff e r e n t k i n d o f a e r o s o l - b a s e d d e t e c t o r f o r H P L C w h i c h c a n b e u s e d i n p a r a l l e l w i t h U V a n d M S d e t e c t i o n . H P L C d e t e c t o r s u s e d i n p h a r m a c e u t i c a l a n a l y s i s a r e i n c r e a s i n g l y p u s h e d t o t h e i r l i m i t s f o r s e n s i t i v i t y a n d u n i v e r s a l d e t e c t i o n . T h e N Q A D u s e s c o n d e n s a t i o n n u c l e a t i o n t e c h n o l o g y t o p r o d u c e a d e t e c t o r w i t h h i g h s e n s i t i v i t y a n d e x c e l l e n t l i n e a r i t y o v e r a w i d e d y n a m i c r a n g e .

T h e p a t e n t e d Wa t e r C o n d e n s a t i o n P a r t i c l e C o u n t e r, t h e h e a r t w i t h i n t h e N Q A D c o n d e n s e s w a t e r v a p o u r o n t o t h e d r i e d p a r t i c l e s f r o m t h e n e b u l i s e r a n d h e a t e d d r i f t t u b e a n d g r o w s t h e m t o a s i z e w h e r e i n d i v i d u a l p a r t i c l e s c a n b e d e t e c t e d e a s i l y u s i n g a n o p t i c a l d e t e c t o r. T h i s t e c h n o l o g y, w h i l s t n e w t o H P L C , h a s b e e n u s e d f o r m a n y y e a r s i n f o r i n s t a n c e s c i e n t i fi c fi e l d s s u c h a s c l i m a t e r e s e a r c h t h e n a n o - - t e c h n o l o g y i n d u s t r y.


A l l aeroso l based HPLC detectors work on the same genera l pr inc ip le . E luent f rom a HPLC co lumn is cont inuous ly sprayed into a mist . The mist i s compromised of smal l ind iv idua l drop lets o f l iqu id at many d iff erent s izes . The s ize d ist r ibut ion of the l iqu id drop lets i s s tab le and repeatab le . The fi gure shows the nebul izat ion process and a graph of the resu l t ing l iqu id drop let s izes .

W h a t i s a n A e r o s o l B a s e d H P L C D e t e c t o r ?


T h e l i q u i d i s e v a p o r a t e d f ro m t h e d ro p l e t s i n t h e m i s t a n d s o l i d re s i d u e i s l e f t b e h i n d a s i n d i v i d u a l p a r t i c l e s s u s p e n d e d i n a i r. W h e n a n a n a l y t e e l u t e s t h e c o l u m n t h e a m o u n t o f s o l i d re s i d u e t h a t re m a i n s a f t e r e v a p o r a t i o n i n c re a s e s . T h e f o l l o w i n g fi g u re s i l l u s t r a t e t h e e v a p o r a t i o n p ro c e s s a n d t h e re s u l t i n g a e ro s o l s i z e d i s t r i b u t i o n s .


The detector uses a sensor that i s ab le to measure the s ize of the aeroso l part ic les . As the s ize of the part ic les increase dur ing e lut ion of ana lytes the detector s igna l detects the sh i f t and outputs the s igna l as a chromatogram.

There are severa l advantages of aeroso l based HPLC detectors over other t rad i t iona l HPLC detect ion techniques. The major i ty o f common HPLC detectors are not cons idered un iversa l in the sense that a spec ifi c property o f the ana lyte is required for the detector to work e .g . a requ irement for a chromophore conta in ing ana lyte for UV detect ion . The l imitat ion for aeroso l based detectors is that the ana lyte must be non-vo lat i le a l though many semi-vo lat i le compounds are a lso detectab le . Otherwise aeroso l based detectors are cons idered to have un iversa l detect ion . Addi t iona l ly there is no d iffi culty us ing grad ient methods as is the case with ref ract ive index (R I ) detectors . Aeroso l based detectors in genera l have good sens i t iv i ty ( low ng to 100ng) and are cost eff ect ive .

Evaporat ive L ight Scatter ing Detector (ELSD), Charged Aeroso l Detector (CAD) are common aeroso l based HPLC detector. that has been commerc ia l ly ava i lab le for severa l decades.


Operat ing Requirements: - D u e t o t h e h i g h s e n s i t i v i t y o f N Q A D t h e c h e m i s t m u s t

c o n s i d e r t h e f o l l o w i n g p a r a m e t e r s t o h a v e a s u c c e s s f u l a n a l y s i s . T h e f o l l o w i n g g u i d e l i n e s a p p l y f o r a n y d e t e c t o r t h a t h a s h i g h s e n s i t i v i t y a n d n e a r u n i v e r s a l d e t e c t i o n c a p a b i l i t y . I t i s i m p o r t a n t t o n o t e t h a t t h e f o l l o w i n g g u i d e l i n e s a r e i n c r e a s i n g l y i m p o r t a n t f o r h i g h p e r f o r m a n c e a n a l y s i s .

S y s t e m c l e a n l i n e s s : H P L C s y s t e m s r e q u i r e fl u s h i n g t o r e m o v e n o n - v o l a t i l e r e s i d u e

f r o m t h e s y s t e m .

O f t e n t h e r e s i d u e t h a t i s p r e s e n t i n t h e s y s t e m d o e s n o t a ff e c t U V-V i s d e t e c t o r s s o i t i s n o t a n o r m a l l y r e q u i r e d p r o c e s s . I n p r a c t i c e t h e m o s t e ff e c t i v e w a y t o fl u s h a s y s t e m i s t o r u n a l l l i n e s a l t e r n a t i n g b e t w e e n h i g h l y p o l a r , n e u t r a l p o l a r i t y , a n d h i g h l y n o n - p o l a r s o l v e n t s . F l u s h i n g t h e s y s t e m i s b e n e fi c i a l a s b o t h p r e v e n t a t i v e m a i n t e n a n c e a n d a f t e r u s i n g n o n - v o l a t i l e b u ff e r s i n t h e s y s t e m .

C h e m i c a l s : T h e l e v e l o f n o n - v o l a t i l e r e s i d u e p r e s e n t i n t h e m o b i l e p h a s e

a ff e c t s t h e l i m i t o f d e t e c t i o n f o r a n a n a l y s i s . M o b i l e p h a s e s t h a t a r e s u i t a b l e f o r L C - M S a n a l y s i s a r e g e n e r a l l y c o m p a t i b l e w i t h N Q A D a n a l y s i s . W h e n u s i n g v o l a t i l e b u ff e r s t h e c h e m i s t m u s t c o n s i d e r t h e l e v e l o f i m p u r i t y i n t h e b u ff e r a n d a s s u m e t h a t a l l i m p u r i t i e s a r e n o n - v o l a t i l e a n d w i l l a ff e c t t h e a n a l y s i s .


Labware : U s e o f d e t e r g e n t s i s n o t r e c o m m e n d e d f o r a n y l a b w a r e u s e d

i n a n a l y s i s p r e p a r a t i o n f o r t h e N Q A D . I f d e t e r g e n t s m u s t b e u s e d t h e c h e m i s t s h o u l d r i n s e w i t h H P L C g r a d e s o l v e n t t o e n s u r e t r a c e r e s i d u e o f d e t e r g e n t h a s b e e n r e m o v e d . T h e c h e m i s t a l s o m u s t c o n s i d e r e x t r a c t i o n o f m a t e r i a l f r o m s a m p l e v i a l s , s e p t u m s e t c . F o r e x a m p l e s o d i u m e x t r a c t e d f r o m g l a s s s a m p l e v i a l s c a n i n t e r f e r e w i t h a n a l y s i s . I n g e n e r a l i t i s r e c o m m e n d e d t h a t t h e c h e m i s t r i n s e s a m p l e v i a l s a n d p i p e t t e s w i t h m o b i l e p h a s e p r i o r t o u s e .

Columns: C o l u m n b l e e d c a n b e a d e t r i m e n t a l s o u r c e o f n o i s e f o r a n

a n a l y s i s . S e l e c t i n g c o l u m n s t h a t a r e s p e c i fi c a l l y l o w b l e e d a r e r e c o m m e n d e d f o r N Q A D . I t i s a l s o i m p o r t a n t t o c o n s i d e r c o l u m n b l e e d a s a f u n c t i o n o f p H o r m o b i l e p h a s e c o m p o s i t i o n w h e n d o i n g g r a d i e n t a n a l y s i s t o m i n i m i z e b a s e l i n e s h i f t s . F o r t r o u b l e s h o o t i n g i t i s r e c o m m e n d e d t o b y p a s s t h e c o l u m n t o d e t e r m i n e t h e e ff e c t o f m o b i l e p h a s e a l o n e t o i s o l a t e c o l u m n s o u r c e s o f b l e e d . A s p a r t o f m e t h o d d e v e l o p m e n t t h e c h e m i s t s h o u l d c o n s i d e r c o l u m n fl u s h i n g t o r e m o v e l a t e e l u t i n g n o n -v o l a t i l e r e s i d u e .

Chemica l Preparat ion : W h e n p r e p a r i n g m o b i l e p h a s e a n d o r s a m p l e s i t i s i m p o r t a n t t o

c o n s i d e r p o t e n t i a l s o u r c e s o f n o n - v o l a t i l e r e s i d u e . U s e o f fi l t e r s m a y i n t r o d u c e n o n - v o l a t i l e c o n t a m i n a t i o n t h a t c a n b e d e t r i m e n t a l t o t h e a n a l y s i s .


WATER CONDENSATION PARTICLE COUNTER:-

I m p o r t a n t i n s t r u m e n t s i n a e r o s o l t e c h n o l o g y a r e C o n d e n s a t i o n Pa r t i c l e C o u n t e r s ( C P C ) .

T h e y a r e u s e d t o m e a s u r e t h e p a r t i c l e n u m b e r c o n c e n t r a t i o n d o w n t o t h e n a n o m e t e r s i z e r a n g e .

T h e l o w e r d e t e c t i o n e ffi c i e n c y i s m u c h l o w e r t h a n i n o p t i c a l p a r t i c l e c o u n t e r s .

T h e p a r t i c l e s a r e e n l a r g e d d u e t o s u p e r s a t u r a t i o n a n d a s u b s e q u e n t c o n d e n s a t i o n o f a c o n d e n s a b l e g a s . T h e p a r t i c l e s r e a c h a s i z e a t w h i c h t h e y c a n b e o p t i c a l l y d e t e c t e d .

T h e n u m b e r c o n c e n t r a t i o n i s m e a s u r e d f o r a l l p a r t i c l e l a r g e r t h a n t h e l o w e r d e t e c t i o n d i a m e t e r.

T h e re a re t w o t y p es o f C PC ` s : -1 . E X PA N S I O N C H A M B E R C P C ( E X T I N C T I O N )2 . C O N T I N U O U S F LO W C P C ( S I N G L E PA RT I C L E )


PRINCIPLE OF WCP COUNTER : - C P C ` s o p e r a t e o n t h e p r i n c i p l e o f e n l a r g i n g s m a l l p a r t i c l e s u s i n g a c o n d e n s a t i o n t e c h n i q u e t o a s i z e t h a t i s l a r g e e n o u g h t o b e d e t e c t e d o p t i c a l l y. A n a e r o s o l s a m p l e i s d r a w n c o n t i n u o u s l y t h r o u g h a c o o l e d s a t u r a t o r a n d t h e n i n t o a h e a t e d c o n d e n s e r w h e r e w a t e r v a p o r d i ff u s e s i n t o t h e s a m p l e s t r e a m . E ff e c t i v e l y, w a t e r d i ff u s e s t o t h e c e n t e r - l i n e o f t h e c o n d e n s e r f a s t e r t h a n h e a t i s t r a n s f e r r e d f r o m t h e w a r m w a l l s , p r o d u c i n g s u p e r s a t u r a t e d c o n d i t i o n s . Pa r t i c l e s t h a t a r e p r e s e n t i n t h e s a m p l e s t r e a m s e r v e a s c o n d e n s a t i o n s i t e s f o r t h e w a t e r v a p o u r. O n c e c o n d e n s a t i o n b e g i n s , p a r t i c l e s g r o w q u i c k l y i n t o l a r g e r w a t e r d r o p l e t s a n d p a s s t h r o u g h a n o p t i c d e t e c t o r, w h e r e t h e y a r e c o u n t e d e a s i l y.

Two of the commerc ia l l y ava i lab le Water CPCs are : -

T S I m o d e l 8 2 W a t e r - b a s e d C P C T S I m o d e l 8 6 U l t r a fi n e W a t e r - b a s e d C P C


Grows seed pa r t i c l e s i n to d rop le t s

• Supersa tu ra t i on occu r s because o f the d iff e rence be tween the the rmo and mass d iff us iv i t i e s o f wa te r vapor

• Coun ts Pa r t i c l e s – Doesn ’ t s i ze them

• 6 Order of magnitude counting range

• 6 O r d e r o f m a g n i t u d e c o u n t i n g r a n g e


T h e a e r o s o l fl o w i s s a t u r a t e d w i t h w a t e r v a p o r a n d t h e t e m p e r a t u r e e q u i l i b r a t e d i n a c o o l e d s a t u r a t o r.

T h e n t h e fl o w p a s s e s t h r o u g h a c o n d e n s e r w i t h h e a t e d w a l l s w h i c h c o n t a i n w a t e r. T h i s p r o d u c e s a n e l e v a t e d v a p o r p r e s s u r e .

E v a p o r a t e d w a t e r v a p o r d i ff u s e s f a s t e r t o t h e c e n t e r o f t h e a e r o s o l s t r e a m t h a n t h e h e a t f r o m t h e w a l l s a n d t h u s s u p e r s a t u r a t e s i t .

T h e p a r t i c l e s a c t a s c o n d e n s a t i o n n u c l e i w h e n l a r g e r t h a n a c t i v a t i o n s i z e a n d g r o w q u i c k l y t o d r o p l e t s o f a d e t e c t a b l e s i z e .

T h e d r o p l e t fl o w i s f o c u s e d i n a n o z z l e a n d i n t r o d u c e d i n t o a c o u n t i n g o p t i c .

T h e d r o p l e t s p a s s a l a s e r b e a m , a n d e a c h s i n g l e p a r t i c l e c r e a t e s a l i g h t p u l s e .

P u l s e s w i t h a n a m p l i t u d e a b o v e a c e r t a i n t h r e s h o l d a r e c o u n t e d .

T h e p a r t i c l e n u m b e r c o n c e n t r a t i o n c a n b e c a l c u l a t e d b y k n o w i n g t h e a e r o s o l fl o w r a t e .


Funct ioning of NQAD : - T h e N Q A D u t i l i z e s a p a r t i c l e c o u n t e r t h a t s e l e c t i v e l y

g r o w s p a r t i c l e s b y c o n d e n s a t i o n o f w a t e r v a p o r. O n l y p a r t i c l e s t h a t a r e a b o v e a c e r t a i n s i z e a r e s u i t a b l e n u c l e a t i o n s i t e s f o r t h e w a t e r v a p o r.

W h e n n o a n a l y t e i s p r e s e n t i n t h e m o b i l e p h a s e a r e l a t i v e l y l o w p e r c e n t a g e o f p a r t i c l e s i n t h e b a c k g r o u n d r e s i d u e a r e l a r g e e n o u g h t o g r o w i n t o d e t e c t a b l e d r o p l e t s . T h e r e m a i n d e r o f t h e p a r t i c l e s r e m a i n t o o s m a l l t o b e d e t e c t e d o p t i c a l l y. W h e n a n a l y t e i s p r e s e n t i n t h e m o b i l e p h a s e t h e n u m b e r o f p a r t i c l e s t h a t a r e l a r g e e n o u g h t o s e r v e a s v a p o r n u c l e a t i o n s i t e s i n c r e a s e s .

T h e N Q A D c o n v e r t s t h e p a r t i c l e c o u n t r a t e i n t o a c h r o m a t o g r a m o u t p u t s i g n a l . B y m e a s u r i n g t h e n e b u l i z e d a e r o s o l u s i n g t h i s t e c h n i q u e v e r y s m a l l s h i f t s i n t h e s i z e o f t h e a e r o s o l d i s t r i b u t i o n c a n b e m e a s u r e d . To t h e a n a l y t i c a l c h e m i s t t h i s t r a n s l a t e s t o h i g h s e n s i t i v i t y a n a l y t e d e t e c t i o n . U n l i ke o t h e r a e r o s o l b a s e d d e t e c t o r s t h e r e i s n o i n t e r f e r e n c e f r o m s e n s o r n o i s e o r d r i f t t h a t c a n i n t e r f e r e w i t h r e s o l u t i o n a n d s e n s i t i v i t y.


SCHEMATIC DIAGRAM OF NQAD:-


N Q A D D I A G R A M :


Nebulization:-

Effl uent f rom the HPLC sys tem i s

nebu l i zed in to a m is t o f u l t r afi ne

d rop le t s .

Evaporation:- The mob i l e phase and add i t i ves evapora te ,

l eav ing beh ind sma l l pa r t i c l e s o f semivo la t i l e o r nonvo la t i l e mate r ia l s . A cho i ce o f evapora to r tempera tu res ensu res mob i le phase evapora t i on wh i l e m in im iz ing evapora t i on o f the ana ly te . The base l ine cu rve rep resen ts the pa r t i c le res idue a f te r evapora t i on o f the pu re mob i l e phase and i t s add i t i ves . The cu rve sh i f t s to a l a rge r s i ze when ana ly te i s p resen t . The magn i tude o f th i s sh i f t co r re la tes to the concen t ra t ion o f ana ly te .


Condensational Growth:-

S u p e r s a t u r a t e d w a t e r v a p o r c o n d e n s e s o n t h e p a r t i c l e s t o f o r m l a r g e d r o p l e t s . O n l y p a r t i c l e s a b o v e a c r i t i c a l s i z e c a n a c t a s c o n d e n s a t i o n n u c l e a t i o n s i t e s , s h o w n h e r e a s t h e W C P C D e t e c t i o n E ffi c i e n c y c u r v e . W h e n u s i n g a m o b i l e p h a s e w i t h v e r y l o w i m p u r i t i e s , t h e b a s e l i n e s i g n a l i s s m a l l c o m p a r e d t o t h e a n a l y t e s i g n a l . A n a l y t e d e t e c t i o n d o w n t o 1 n g a n d b e l o w i s p o s s i b l e .


Optical Detection:- The d rop le t s a re de tec ted in d i s c re te f o rm

as they pass th rough the l ase r beam o f an op t i ca l de tec to r. I nd iv idua l l i gh t pu l ses measu red by the pho tode tec to r have a h igh s igna l - to -no i se ra t i o , mak ing i t i n sens i t i ve to pho tode tec to r background no i se o r l a se r d r i f t . The dynamic range o f the u l t rasens i t i ve de tec to r i s ove r f ou r o rde rs o f magn i tude .

What Makes the NQAD Detector Better?Broad Range of Analytes UltraSensitivity at LowNanogram LevelWide Dynamic Range Linear Response Reproducible Results Small Size, Robust, Reliable Easy Set-Up and Operation


Broad Range of Analytes: T h e d e t e c t i o n o f t h e N Q A D

d e t e c t o r i s n e a r u n i v e r s a l f o r c o m p o u n d s t h a t a re l e s s v o l a t i l e t h a n t h e m o b i l e p h a s e . C h ro m o p h o re s a n d fl u o ro p h o re s a re n o t n e e d e d f o r d e t e c t i o n , t h e re b y e l i m i n a t i n g o r d e c re a s i n g t h e n e e d f o r c o m p o u n d d e r i v e r t i z a t i o n . T h i s fi g u re s h o w s fi v e d i ff e re n t g ro u p s o f c o m p o u n d s d e t e c t e d b y t h e d e t e c t o r . Ru n t i m e f o r t h e a n a l y s e s r a n g e d f ro m 5 t o 1 5 m i n u t e s . T h e d e t e c t o r ’ s f a s t re s p o n s e t i m e p ro d u c e s n a r ro w p e a k s f o r m o re a c c u r a t e q u a n t i fi c a t i o n a n d e n h a n c e d re s o l u t i o n .


Ultra-Sens i t ive to Low Nanogram Levels :

W i t h t h e a b i l i t y t o d e t e c t s u b - n a n o g r a m l e v e l s , t h e d e t e c t o r ’ s u l t r a - h i g h s e n s i t i v i t y c a n b e u s e d w h e n o n l y t r a c e a m o u n t o f a n a l y t e s a r e a v a i l a b l e . T h e d e t e c t o r i s i d e a l f o r s e a r c h i n g f o r d r u g i m p u r i t i e s , d e g r a d a t i o n p r o d u c t s , e x c i p i e n t s a n d w h e n i n d u s t r i a l h y g i e n e i s a c o n c e r n . B o t h p r e v i o u s l y e a s y a n d h a r d - t o - m e a s u r e c o m p o u n d s c a n b e q u a n t i fi e d a c c u r a t e l y w i t h m i n i m a l s a m p l e p r e p a r a t i o n . S h o w n h e r e a r e 0 . 5 n g c a t i o n c o n c e n t r a t i o n s w i t h p e a k s t h a t h a v e s i g n a l - t o - n o i s e r a t i o s h i g h e r t h a n 1 0 : 1 .


Wide Dynamic Range:

The w ide dynamic range

shows a l i nea r response cove r ing ove r f ou r o rde rs o f magn i tude . Wi th th i s w ide range le ss samp le p repara t ion t ime i s requ i red and more in fo rmat ion i s ob ta ined f rom a s ing le samp le so lu t i on i n jec t i on .


Linear Response: T h e d e t e c t o r s h o w s s u p e r i o r

l i n e a r i t y c o m p a r e d t o o t h e r a e r o s o l - b a s e d d e t e c t o r s , c o v e r i n g s e v e r a l o r d e r s o f m a g n i t u d e f o r m o s t a n a l y t e s . W h e n y o u c o m b i n e i t s s e n s i t i v i t y a n d l i n e a r r e s p o n s i v e n e s s , m u l t i p l e s a m p l e p r e p a r a t i o n i s o f t e n n o t n e c e s s a r y ; o n l y o n e s a m p l e p r e p a r a t i o n m a y b e u s e d f o r t h e m a i n d r u g c o m p o u n d , i m p u r i t i e s a n d / o r d e g r a d a t i o n p r o d u c t s a n a l y s i s . O n l y o n e m e t h o d v a l i d a t i o n f o r b o t h t h e m a i n d r u g c o m p o u n d a n d o t h e r c o m p o u n d s p r e s e n t i n t r a c e a m o u n t s i s r e q u i r e d . T h i s fi g u r e s h o w s a p o r t i o n o f S u c r o s e l i n e a r i t y r a n g e .


Reproducible Results:

D e t e c t o r re s p on s e i s s t a b l e , p re c i s e a n d re p rod u c i b l e f o r re l i a b l re s u l t s . To d e m on s t r a t e t h i s , s i x c h rom a t o g r a m s o f a s o l u t i on c on t a i n i n g L i + , N a + , a n d K + w e re ob t a i n e d on d i ff e re n t d a y s a n d c o m p a re d . T h e fi g u re d e m on s t r a t e s t h e c l o s e n e s s o f t h e d e t e c t o r re s p on s e s on d i ff e re n t

d a ys ; t h e y a re i d e n t i c a l .


Small Size, Robust, Reliable: We igh ing i n a t j u s t 20 lbs ( 9 .1 kg ) and w i th a

f o o tp r i n t o f j u s t 6 i n c hes x 17 i nc hes

( 15 .5 c m x 43 c m) , t he de tec to r i s qu i te po ss i b l y t he sma l l e s t HPLC de tec to r o n

t he marke t . Bu t do n ' t l e t i t s d im inu t i ve s ta tu re f o o l yo u . Pac ked i n s i de i s mo re

o f eve ry th i ng yo u ' re l o o k i ng f o r - s ens i t i v i t y , dynamic range , l i nea r i t y ,

rep ro duc ib i l i t y , un i ve r sa l de tec t i o n - a l l a t an aff o rdab le p r i c e .

Easy Set-Up and Operation:


ADVANTAGES OF NQAD:-

Uses water as the condensing fl uid – non-toxic , odor less, non-fl ammable, non-contaminat ing

Ultra-sensit ive particle size range – f rom 2.5 nm to over 3 µm diameter

Wide dynamic concentration range – f rom 0 to 10 7 part ic les/cm 3


In various fi elds:

Agr i cu l tu re /Food /Bevarages

Env i ronment

Energy /pet ro leum

Fo rens i cs /Narcot i c s

A n a l y s i s o f c o m p o u n d s :

A m i n o a c i d s

C a r b o h y d r a t e s

S t e r o i d s

C a ff e i n e

C a t i o n s

C h o l e s t e r o l

A m i n e

A r t e m i s i n i n a n d D i h y d r o a r t e m i s i n i n

P E G 1 0 0 0 a n d P E G 2 0 0 0 0

S u l f o n i c A c i d a n d S u l f a n i l a m i d e

S a c c h a r i n , T h e o p h y l l i n e a n d S u c r o s e

O v a l b u m i n

U S E S O F N Q A D : -In various fi elds:

Agr i cu l tu re /Food /Bevarages

Env i ronment

Energy /pet ro leum

Fo rens i cs /Narcot i c s

U S E S O F N Q A D : -

Analysis

ofcompounds: A m i n o a c i d s

C a r b o h y d r a t e s

S t e r o i d s

C a ff e i n e

C a t i o n s

C h o l e s t e r o l

A m i n e

A r t e m i s i n i n a n d D i h y d r o a r t e m i s i n i n

P E G 1 0 0 0 a n d P E G 2 0 0 0 0

S u l f o n i c A c i d a n d S u l f a n i l a m i d e

S a c c h a r i n , T h e o p h y l l i n e a n d S u c r o s e

O v a l b u m i n


C O N C LU S I O N : - These data demonstrates that the NQAD is an at t ract ive a l ternat ive /add i t ion to ana lyt ica l laborator ies . The subnanogram sens i t iv i ty coupled with a wide l inear /dynamic range a l lows for the s imultaneous detect ion of the main ana lyte peak and impur i t ies /degradat ion produts /exc ip ients , espec ia l ly those that do not conta in a chromophore/fl urophore. H igh reproduc ib i l i ty i s t ip ica l , which g ives the chromatographer run to run assurance. A major advantage of NQAD in compar is ion to other aeroso l based detectors is i t s u l t ra fast HPLC compatab i l l i ty which dramit ica l ly decreases waste and increases produc ib i l l i ty .


References:M.L. Kearns, L . Magnusson, W. Gou, A .

Brenner, J .A .Koropchak, and D.S. R is ley, “Determinat ion of Weak UV-Absorb ing Drug Substances Us ing Cap i l lary Electrophores is wi th Condensat ion Nuc leat ion L ightScatter ing Detect ion” , LC-GC, 19(6) (2001) 624-632

L. A l len and J .A . Koropchak, “Condensat ion Nuc leat ion L ight Scatter ing: A New Approach to Development of H igh Sens i t iv i ty, Un iversa l Detectors for Separat ions” ,Ana lyt ica l Chemistry, 65 (1993) 841-844

L.B. A l len , J .A . Koropchak and B. Szostek, “Condensat ion Nuc leat ion L ight Scatter ing Detect ion for Convent iona l Reversed-Phase L iqu id Chromatography”, Ana lyt ica l Chemistry, 67 (1995) 659-666

J .A . Koropchak, C .L . Heenan and L .B. A l len , “D irect Compar ison of Evaporat ive L ight Scatter ing and Condensat ion Nuc leat ion L ight Scatter ing Detect ion for L iqu id Chromatography”, Journa l o f Chromatography, 736 (1996) 11-19


J .A . Koropchak , S . Sada in , X . Yang , L . Magnusson ,“Nanopar t i c le Detec t ion Methods fo r Chemica l Ana lys i s” ,Ana ly t i ca l Chemis t ry, 71 (1999) 386A-394A

J .A . Koropchak , S . Sada in , X . Yang , L . Magnusson ,

M. Heybroek , M . An is imov, “Fundamenta l Aspects o f Aeroso l -based L ight Scat te r ing fo r Separat ions Detec t ion” , in Advances in Chromatography, 40 , Chapter 5 (2000) 275 -314 .

M.M. Wa ich igo and J . Koropchak , “Eva luat ion o f the Per fo rmance o f a Pro to type Condensat ion Nuc leat ion L ight Scat te r ing Detec tor fo r HLPC Ut i l i z ing Nanopure Water as Condens ing F lu id” , Poste r p resentat ion a t P i t t con Confe rence & Expo , Ch icago , I L , February 25 -March 2 (2007) .

C .R . M i t che l l , “Compar i son o f Three Un iversa l

Evaporat ive Aeroso l Detec tors fo r HPLC” , Poste r p resentat ion a t HPLC , Ba l t imore , MD, May 10 -16 (2008)

C . B rune l l i , H . J upe , R . Szucs , P. Sandra , M . Hanna -Brown, “Compared Un iversa l Detec t ion fo r Pharmaceut i ca l Ana lys i s o f Non -chromophor i c Compounds : Poss ib i l i t i es and L im i ta t ions o f Evaporat ive Detec tors” , Poste r p resentat ion a t HPLC , Ba l t imore , MD, May 10 -16 (2008)

C . B i l l e , D . Ober re i t , L . Kyar iga , “A New HPLC

Detec tor – U t i l i z ing Condensat ion Nuc leat ion Techno logy” . Pos te r p resentat ion a t Ana ly t i ca , Mun ich Germany, Apr i l 1 -4 (2008)

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