Capillary zone electrophoresis , drug

Gotti et al. [42] reported an analytical study of penicillamine in pharmaceuticals by capillary zone electrophoresis. Dispersions of the drug (0.4 mg/mL for the determination of (/q-penicillaminc in water containing 0.03% of the internal standard, S -met hy I - r-cystei ne, were injected at 5 kPa for 10 seconds into the capillary (48.5 cm x 50 pm i.d., 40 cm to detector). Electrophoresis was carried out at 15 °C and 30 kV, with a pH 2.5 buffer of 50 mM potassium phosphate and detection at 200 rnn. Calibration graphs were linear for 0.2-0.6 pg/mL (detection limit = 90 pM). For a more sensitive determination of penicillamine, or for the separation of its enantiomers, a derivative was prepared. Solutions (0.5 mL, final concentration 20 pg/mL) in 10 mM phosphate buffer (pH 8) were mixed with 1 mL of methanolic 0.015% 1,1 -[ethylidenebis-(sulfonyl)]bis-benzene and, after 2 min, with 0.5 mL of pH 2.5 phosphate buffer. An internal standard (0.03% tryptophan, 0.15 mL) was added and aliquots were injected. With the same pH 2.5 buffer and detection at 220 nm, calibration graphs were linear for 9.3-37.2 pg/mL, with a detection limit of 2.5 pM. For the determination of small amounts of (L)-penicillamine impurity, the final analyte concentration was 75 pg/mL, the pH 2.5 buffer contained 5 mM beta-cyclodextrin and 30 mM (+)-camphor-10-sulfonic acid, with a voltage of 20 kV, and detection at 220 nm. Calibration graphs were linear for 0.5-2% of the toxic (L)-enantiomer, with a detection limit of 0.3%. 

Nishi et al. [110] used dextran and dextrin as chiral selectors in capillary-zone electrophoresis. Polysaccharides such as dextrins, which are mixtures of linear a-(l,4)-linked D-glucose polymers, and dextrans, which are polymers of D-glucose units linked predominantly by a-(l,6) bonds, have been employed as chiral selectors in the capillary electrophoretic separation of enantiomers. Because these polymers are electrically neutral, the method is applicable to ionic compounds. The enantiomers of basic or cationic drugs such as primaquine were successfully separated under acidic conditions. The effects of molecular mass and polysaccharide concentration on enantioselectivity were investigated. 

Finally, work that may facilitate understanding the role of oq-acid glycoprotein variants in inter-individual variations in plasma protein binding, pharmacokinetic behavior, and drug action has been described. A capillary zone electrophoresis method that allows for the determination of 11 intact forms (i.e., isoforms, glycoforms) of oq-acid glycoprotein has been described [84],... 

After a short introduction into the relevance of Impurity profiling for regulatory authorities, public health, and the pharmaceutical industry, an overview is presented based on the various modes of capillary electrophoresis that have been used in drug impurity analysis. The applications of capillary zone electrophoresis, non-aqueous capillary electrophoresis, micellar electrokinetic capillary chromatography, microemulsion electrokinetic capillary chromatography, capillary gel electrophoresis, and capillary electrochromatography are presented consecutively. 

Vassort, A., Barrett, D. A., Shaw, P. N., Ferguson, P. D., and Szucs, R. (2005). A generic approach to the impurity profiling of drugs using standardised and independent capillary zone electrophoresis methods coupled to electrospray ionisation mass spectrometry. Electrophoresis 26, 1712—1723. 

Tagliaro, F., Smith, F. P., Turrina, S., Equisetto, V., and Marigo, M. (1996). Complementary use of capillary zone electrophoresis and micellar electrokinetic capillary chromatography for mutual confirmation of results in forensic drug analysis. /. Chromatogr. A 735, 227—235. 

Reilly, J., and Saeed, M. (1998). Capillary electrochromatography as an alternative separation technique to high-performance liquid chromatography and capillary zone electrophoresis for the determination of drug related impurities in Lilly compound LY300164. /. Chromatogr. A 829, 175-186. 

Dedicated applications of capillary zone electrophoresis (CZE) coupled to MS are discussed, particularly in the field of drug analysis. Development of other capillary-based electrodriven separation techniques such as non-aqueous capillary electrophoresis (NACE), micellar electrokinetic chromatography (MEKC), and capillary electrochromatography (CEC) hyphenated with MS are also treated. The successful coupling of these electromigration schemes with MS detection provides an efficient and sensitive analytical tool for the separation, quantitation, and identification of numerous pharmaceutical, biological, therapeutic, and environmental compounds. 

Capillary zone electrophoresis (CZE) is the most common electrophoretic separation technique due to its simplicity of operation and its flexibility. It is the standard mode for drug analysis, identification of impurities, and pharmacokinetic studies. Other separation modes, such as capillary isotachopho-resis (CITP), micellar electrokinetc chromatography (MEKC), capillary electrochromatography (CEC), capillary gel electrophoresis (CGE), capillary isoelectric focusing, and affinity capillary electrophoresis (ACE), have then-advantages in solving specific separation problems, since the separation mechanism of each mode is different. 

Plasma protein binding is also an important parameter in the pharmacokinetic field. Frontal analysis combined with capillary zone electrophoresis (CZE-FA) (67-69) is a powerful technique for high-throughput assay, because it is relatively rapid and easy to automate, in comparison with conventional methods such as dialysis, ultrafiltration, and ultracentrifugation. Recently, we introduced the EKC approach with ionic CDs to frontal analysis for anionic drugs that cannot be analyzed by conventional CZE-FA (70). In this approach, ionic CDs work as an EKC pseudostationary not for proteins but for small solutes. 

JC Kraak, S Busch, H Poppe. Study of protein-drug binding using capillary zone electrophoresis. J Chromatogr 608 257-264, 1992. 

MG Quaglia, E Bossu, C DellAquila, M Guidotti. Determination of the binding of a /32-blocker drug, frusemide and ceftriaxone to serum proteins by capillary zone electrophoresis. J Pharm Biomed Anal 15 1033—1039, 1997. 

XX Zhang, F Hong, WB Chang, YX Ci, YH Ye. Enantiomeric separation of promethazine and D,L-a-amino-/3-[4-(l,2-dihydro-2-oxo-quinoline)] propionic acid drugs by capillary zone electrophoresis using albumins as chiral selectors. Anal Chim Acta 392 175-181, 1999. 

J Haginaka, N Kanasugi. Separation of drug enantiomers by capillary zone electrophoresis using ovoglycoprotein as a chiral selector. J Chromatogr A 782 281-288, 1997. 

F Kilar. Stereoselective interaction of drug enantiomers with human serum transferrin in capillary zone electrophoresis. Electrophoresis 17 1950-1953, 1996. 

A Amini, U Paulsen-Sorman. Enantioseparation of local anaesthetic drugs by capillary zone electrophoresis with cyclodextrins as chiral selectors using a partial-filling technique. Electrophoresis 18 1019-1025, 1997. 

Eberle et al. [134] separated the enantiomers of omeprazole and structurally related drugs by capillary zone electrophoresis with bovine serum albumin as chiral selector. The separations were carried out on a fused silica column (60 cm x 50 pm, 50 cm to detector) with a buffer consisting of 100-/zM-bovine serum albumin and 7% 1-propanol in 10 mM potassium phosphate pH 7.4. Electrokinetic injection was at 5-8 kV for 7 s. An applied voltage of 300 V/cm was used. Detection was at 290 nm. Detection limits were 0.04 mg/ml for the analytes studied. 

Lin et al. [52] reported simultaneous determination of vigabatrin and gabapentin in pharmaceutical preparations by simple capillary zone electrophoresis after derivatization with ofloxacin acyl chloride (OAC) with UV detection at 300 nm. The assay was rectilinear for both drugs over the concentration range of 50-500 /iM and the lower limit of detection was 5 /iM. Both the within-day and day-to-day reproducibilities and accuracies are below 3.1% and 4.8%, respectively. 

W. Steuer, I. Grant, and F. Erni, Comparison of high-performance liquid chromatography, Supercritical fluid chromatography and capillary zone electrophoresis in drug analysis, J. Chromatogr., 507 125 (1990). 

S. Fanali, M. Cristalli, and A. Nardi, Capillary zone electrophoresis for drug analysis rapid determination of minoxidil on pharmaceutical formulations, Farmaio, 47 1 (1992). 

Gottardo R, Polettini A, Sorio D, Pascali JP, Bortolotti F, Liotta E, Tagliaro F (2008) Capillary zone electrophoresis (CZE) coupled to time-of-flight mass spectrometry (TOF-MS) applied to the analysis of illicit and controlled drugs in blood. Electrophoresis 29(19) 4078 1087. doi 10.1002/elps.200800087... 

CE has many separation modes that are beneficial to protein impurity analysis. Within the many thousands of potential protein impurities in a recombinant product there will be several that have only minor physicochemical differences from the drug product. The application of different CE modes can potentially resolve these impurities. CE methods can be divided into four principle modes that are applicable to recombinant protein impurity analysis capillary zone electrophoresis, capillary isoelectric focusing, capillary gel electrophoresis, and micellar electrokinetic capillary chromatography. Each mode will be discussed briefly. Since the technology is so young and still very exploratory, CE methods are developed empirically for specific separations. It is difficult to provide standard protocols for CE impurity analysis. Instead, protocols that can be used as a starting point for impurity analysis will be provided as well as the citation of examples of impurity analyses from the literature to provide additional sources of protocols for interested readers. 

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