Porous graphitic carbon (PCC) is a strong reversed-phase absorbent with retention characteristics similar to those of alkyl bonded silicas, e.g. octadecylsilane (ODS)im4. However, unlike silica gel it offers a number of critically important advantages. These include the absence of residual silanol groups, which can give rise to problems with the elution of amines, insolubility in aggressive aqueous-organic mobile phases at extreme pH values, a homogeneous surface and a reproducible performance from batch to batch. Polymeric packing materials also offer some of these advantages but suffer from other problems such as limited mechanical stability and poorer mass transfer properties. PGC columns would appear, therefore, to offer unique properties which would commend them particularly to the analysis of basic compounds of pharmaceutical interest. The number of literature applications with PGC columns is still, however, very small.
The determination of tioconazole and three very closely structurally related potential impurities is the subject of a monograph in the United States Pharma-copoeia5. However, the separation is difficult to achieve with ODS reversed-phase columns, requiring long elution times and an aggressive mobile phase (leading to short column lifetimes and requiring that a solvent conditioning pre-column be included). In addition the major hydrolysis product of tioconazole is unretained and cannot be determined. The analysis of tioconazole has been the subject of further investigation and optimisation 637 from which it was concluded that a phenyl-bonded silica with an ion-pairing mobile phase provided optimum selectivity within the constraints of a non-aggressive mobile phase. However, it was further shown that to achieve optimised resolution of the low levels expected of the potential impurities it was necessary to modify the detection wavelength from 219 nm, as specified in ref. 5, to 260 nm'. This shift to longer wavelength places increased demands upon the detector performance and makes the detection of low levels of the hydrolytic degradation product more difficult.
This paper describes the use of a PGC column to separate tioconazole from the three potential impurities and its main hydrolytic degradation product. It is also shown that the enhanced selectivity offered by the PGC column permits the use of low wavelength detection.