Bioanalysis chiral

A. Walhagen and L.-E. Edholm, Chiral separation on acliiral stationary phases with different functionalities using /3-cyclodextiin in the mobile phase and application to bioanalysis and coupled columns , Chromatographia 32 215-223 (1991). 

Capillary electrophoresis is still in a state of evolution and a technique of choice for certain applications (chiral analysis small ion analysis in food and beverage industries bioanalysis). The number of reviews [365,858,884,889-896], books and manuals [365,897-903] published on (HP)CE/CEC/CZE in the last decade is overwhelming, in particular in relation to the importance of the technique (see also Bibliography). CE-LIFS has been reviewed [904]. 

Dr. Bhushan is a Member of Editorial Board of Biomedical Chromatography, (John Wiley Sons, UK, since Jan 1996) Bioanalysis (Future Science Group, UK, Since 2011), and Acta Chromatographica (Akademiai Kiado, Hungary, since 2012). He edited four Special Issues of Biomedical Chromatography on Chiral Resolutions as Guest Editor. 

The progress toward enantiomerically pnre drngs makes the selective and rapid analysis of enantiomers an important issue, both for chiral parity determinations and for enantioselective bioanalysis. Chankvetadze et al. [198] performed enantioseparations within an analysis time of 1 min for each of two chiral compounds (1,2,2,2-tetraphenylethanol and 2,2 -dihydroxy-6,6 -dimethylbiphenyl) by nsing a homemade capillary column containing monolithic silica modified with amylose tris(3,5-dimethylphenylcarbamate) (Figure 17.10). 

W. J. Lough and T. A. G. Noctor, Multi-column approaches to chiral bioanalysis by liquid chromatography , Prog. Pharm. Biomed, Anal. 1 241 -257 (1994). 

Pure organic mobile phases, as applied in normal-phase LC (NPLC) and with some chiral stationary phases (Chiralpak AD and AS, Ch. 1.4.3), are generally not applicable in LC-ESI-MS. Post-colunm addition of a mixture of 5 mmolA aqueous ammonium acetate and methanol or 2-propanol is required. The alcohol assures miscibility with the organic solvent [89]. Examples of chiral NPLC-MS for quantitative bioanalysis are discussed in Ch. 11.7.4. Post-colunm addition of the aqueous phase via a sheath liquid interface has been proposed [90]. 

Methylphenidate (MPH, Ritalin ) is a central nervous system stimulant that is used for the treatment of attention deficit disorders, with and without hyperactivity, and narcolepsy. MPH has two chiral centres and is marketed as a racemic mixture. It is known that d-threo-MP is pharmacologically more active than l-threo-MPH. The drag is rapidly metabohzed in humans to the inactive ritalinic acid. High-throughput analysis with chiral selectivity is demanded for the bioanalysis of MPH and its major metabolite. 

The group of Bakhtiar [57-59] described the chiral bioanalysis of MPH in various matrices, utilizing a number of sample pretreatment strategies, separation on a Chirobiotic V columns, and the use of positive-ion APCI-MS in SRM mode. The chiral selectivity of the Chirobiotic V column is based on the use of the macrocyclic glycopeptide antibiotic vancomycin. The column can be used in both aqueous and organic mobile phase. 

The second general approach to overcome poor reverse-phase retention is to employ NP-LC. By comparison to RP-LC, the historic use of NP-LC for bioanalysis is negligible because of several limitations. The most notable limitation is the inability to perform reproducible gradient elution. Nevertheless, NP-LC can be a viable option for analytes too polar for RP-LC and produces far less back pressure. Perhaps, the most visible application of NP-LC is for the bioanalysis of chiral drugs [96]. This critical niche is largely the result of the frequent use of NP mobile phases with chiral stationary phases. 

Chiral GC was under development and was being used successfully, for example for chiral dmg bioanalysis, at the same time as commercialised CSP for LC were breaking through. The technique received a boost when cyclodextrin GC phases came onto the market. However, with most drug bioanalysis being carried out by LC, and LC-MS in particular, chiral GC is more the preserve of application areas such as the analysis of odourous compounds [24] and the field of insect pheromones [25]. 

Wikberg, T. Korkolainen, T. Karlsson, M. Enantiomeric bioanalysis of simendan and levosimendan by chiral high-performance liquid chromatography, Chirality, 1996,8, 511-517. 

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