Separation methods for acyclovir and related antiviral compounds

摘要

Acyclovir(ACV) is an antiviral drug, which selectively inhibits replication of members of the herpes group of DNA viruses with low cell toxicity. Valaciclovir(VACV), a prodrug of ACV is usually preferred in the oral treatment of viral infection, mainly herpes simplex virus(HSV). Also other analogues such as ganciclovir and penciclovir are discussed here,. The former acts against cytomegalovirus(CMV) in general and the latter against CMV retinitis. The action mechanism of thee antiviral drugs is presented briefly here, mainly via phos0horylation and inhibition of viral DNA polymerase. The therapeutic use and the phartmacokinetics are also outlined. The measurement of the concentration of acyclovir and related compounds n biol9gical samples poses a particularly significant challenge because these drugs tend to be structurally similar to endogenous substances., The analysis requires the use of highly selective analytical techniques and chromtography methods are a first choice to determine drug content in pharmaceuticals and to measure them in body fluids. Chromatography can be considered the procedure of choice for the bio-analysis of this class of antiviral compounds , as this methodology is characterised by goo specificity an accuracy and it is particularly useful when metabolites need to be monitored. Among chromatographic techniques, the reversed-phase(RP)HPLC is widely used for the analysis. C_(18) Silica columns form 7.5 to 30 cm in length are sued, the separation is carried out mainly at room temperature and less than 10 min is sufficient for the analysis at 1.0-1.5 ml/min of flow-rate. The separation methods require an isocratic system, and various authors have proposed a variety of mobile phases,. The detection requires absorbance or fluorescence measurements carried out at 250-245 nm and at #gamma#_(ex)=260-285 nm, respectively. The detection limit is about 0.3-10 ng/ml but the most important aspect is related to the sample treatment, mainly when boy fluids are under examination. The plasma samples obtained from human blood are pre-treated with an acid or acetonitrile deproteinization and the supernatant after centrifugation is successively extracted before RP-HPLC injection. Capillary Electrophoresis methods are also discussed. This new analytical approach might be the expected evolution, in fact the analyses are improved with regard to time and performance, in particular coated capillary as well as addition of stabilisers have been employed. The time of analysis is shortened arriving at less that half a minute. Furthermore by suing an electrochemical detection, and having a calibration linearity in the range of 0.2-20.0 ng/ml, the detection limit is 0.15#mu#g/ml. The measurement of acyclovir and penciclovir have been presented but in the future other related drugs will probably be available using CE methods