Zirconia-based Stationary Phases Research Articles

Fast and efficient zirconia-based reversed phase chromatography for selective determination of triptans in rat plasma

Selective and fast chromatographic method was essential for the determination of triptans, selective serotonin receptor (5-HT1) agonists, in biological specimens. However, selective chromatographic separation of these highly basic drugs is a challenging problem on silica-based stationary phases. Zirconia-based stationary phases have been introduced as an efficient alternative for silica-based columns offering unique stability, selectivity, and retention ability for various classes of drugs. Herein, a new selective, fast and reproducible high performance liquid chromatographic method (HPLC) was developed and validated for the determination of four triptans in plasma samples namely; Sumatriptan (SMT), Zolmitriptan (ZLT), Eletriptan (ELT) and Rizatriptan (RZT). Zirconia-based polybutadiene (PBD) column was used for the separation and quantitation of the studied triptans in rat plasma based on mixed mode ion exchange and reversed phase chromatography. Zirconia-PBD column (ZirChrom-PBD) has enhanced chemical and thermal stability, selectivity and provides high resolution for the investigated triptans in short analysis time compared with the commonly used C18 columns. A simple isocratic separation mode was used with a mobile phase consisted of acetonitrile and 10mM phosphate buffer adjusted to pH 3.0 (20:80; v/v) at flow rate 1.0mLmin−1. The column was maintained at 50°C and effluent was monitored by photodiode array detector (PDA). The developed method was validated in agreement with US-FDA guidelines and was appropriate for analysis of triptans in plasma samples. The linearity range obtained for the developed HPLC method was 15–2000ngmL−1 with detection limits of 4.8- 6.2ngmL−1 for all the studied triptans. The developed zirchonia-PBD-HPLC method was applied successfully to study the pharmacokinetics of ZLT in rats after a single oral dose. The method was proved to be valuable for therapeutic drug monitoring and bioavailability studies of the studied triptans.

The Retention Behavior of Acidic, Basic and Neutral Pharmaceuticals on the Deactivated Polybutadiene Zirconia Phase

Reversed zirconia-based stationary phases belong among interesting alternatives of widely used RP silica phases. Zirconia displays specific surface properties, which are responsible for a unique retention mechanism. Furthemore, it is necessary especially for acidic analytes to add a strong Lewis base to the mobile phase mainly to improve the separation efficiency. However, commonly recommended strong Lewis base buffers are not volatile and therefore are incompatible with a mass spectrometric detection. A novel RP zirconia-based stationary phase with deactivated Lewis acid sites of zirconia was introduced to enable the use of volatile additives (acetate, formate) despite their low Lewis basicity. It is reported on the influence of surface deactivation on chromatographic behavior of acidic, basic and neutral analytes in this paper. The influence of variables such as pH levels, Lewis base type, its concentration and temperature were studied. The results were compared with the undeactivated stationary phase. In general, around 2.5-fold stronger retention of compounds was observed on the deactivated phase. Moreover, some variances in retention and selectivity were observed for both acidic and basic analytes when using different Lewis bases. For these reasons the properties of deactivated and unmodified phases under the same conditions were partly diverse and consequently the selectivity was similar but not identical.

Zirconia-Based Stationary Phases for Chiral Separation: Mini Review

Separation of enantiomers is one of the most interesting and challenging tasks in the field of separation science. High-performance liquid chromatography (HPLC) and recently capillary electrochromatography (CEC) using chiral stationary phases (CSP) are two of the most useful techniques for both enantioseparation and determination of enantiomeric composition. Although silica has been extensively used as the base material for the stationary phases due to attractive properties including desirable mechanical strength, surface characteristics, catalytic inertness, and surface derivatization possibilities, it has some inherent shortcomings including the narrow range of pH and thermal stability. The zirconia-based stationary phases have shown excellent performance in the separation of wide range of compounds and have been considered as an alternative to silica-based stationary phases due to desirable chemical and physical properties such as resistance to thermal conditions, resistance to extreme pHs, and mechanical stability. Recently, zirconia-based CSPs in either particle-packed or monolithic columns have received considerable attention. This mini-review reports the development and applications of zirconia based stationary phases for chiral separations by HPLC and CEC.

The retention behaviour of polar compounds on zirconia based stationary phases under hydrophilic interaction liquid chromatography conditions

The most separations in HILIC mode are performed on silica-based supports. Nevertheless, recently published results have indicated that the metal oxides stationary phases also possess the ability to interact with hydrophilic compounds under HILIC conditions. This paper primarily describes the retention behaviour of model hydrophilic analytes (4-aminobenzene sulfonic acid, 4-aminobenzoic acid, 4-hydroxybenzoic acid, 3,4-diaminobenzoic acid, 3-aminophenol and 3-nitrophenol) on the polybutadine modified zirconia in HILIC. The results were simultaneously compared with a bare zirconia and a silica-based HILIC phase. The mobile phase strength, pH and the column temperature were systematically modified to assess their impact on the retention of model compounds. It was found that the retention of our model hydrophilic analytes on both zirconia phases was mainly governed by adsorption while on the silica-based HILIC phase partitioning was primarily involved. The ability of ligand-exchange interactions of zirconia surface with a carboxylic moiety influenced substantially the response of carboxylic acids on the elevated temperature as well as to the change of the mobile phase pH in contrast to the silica phase. However, no or negligible ligand-exchange interactions were observed for sulfanilic acid. The results of this study clearly demonstrated the ability of modified zirconia phase to retain polar acidic compounds under HILIC conditions, which might substantially enlarge the application area of the zirconia-based stationary phases.

RP-ZrO2 Stationary Phase as an Alternative to Separate of Doxazosin Impurities

Degradation products and related compounds occurring in drugs as impurities have often very similar properties as the parent substance. Therefore new analytical separation methods which show appropriate selectivity are required. Apart from improvements on silica-based reversed phases the attention has also been focused on other materials such as modified inorganic supports. In this study a polystyrene-coated zirconia was examined as an alternative in analysis of parent drug (doxazosin) and its impurities. Doxazosin and its five pharmacopoeial impurities were separated within 16 min. The suitability of the developed method was verified and confirmed by means of linearity, precision, inter-day precision, robustness and determination of LOD as well as LOQ. The results proved the potential of zirconia-based stationary phases to be useful alternatives in the field of drug analysis.

Utilization of zirconia stationary phase as a tool in drug control

Zirconia-based stationary phases represent an interesting alternative to silica-based materials. Two zirconia-based stationary phases were studied as an option for use in drug analysis. The different properties of zirconia material, distinct from RP silica-columns, were employed for the development of a novel and rapid stability monitoring HPLC method. This method enables simultaneous control of possible degradation processes of active substance (ibuprofen) as well as antimicrobial excipients (methyl-and propylparaben). The separation of ibuprofen, its two main degradation products 2-(4-isobutyrylphenyl)propionic acid and 4-isobutylacetophenone, parabens, and 4-hydroxybenzoic acid as their degradation product was successfully accomplished on a Zr-CarbonC18 column using a mobile phase consisting of acetonitrile-phosphate buffer (pH 4.8)-propan-2-ol (27:56:17, v/v/v). Detection was performed at 258 nm and the analysis was completed within 17 minutes.

Mixed-mode reversed-phase and ion-exchange separations of cationic analytes on polybutadiene-coated zirconia

The retention and selectivity of the chromatographic separation of basic (cationic) analytes on a polybutadiene-coated zirconia (PBD–ZrO 2) stationary phase have been studied in greater detail than in previous studies. These separations are strongly influenced by the chemistry of the accessible surface of zirconia. In the presence of buffers which contain hard Lewis bases (e.g., phosphate, fluoride, carboxylic acids) zirconia’s surface becomes negatively charged due to adsorption of the buffer anion at the hard Lewis acid sites. Consequently, under most conditions (e.g., neutral pH), cationic analytes undergo both hydrophobic and cation-exchange interactions. This mixed-mode retention process generally leads to greater retention factors for cations relative to those on silica-based reversed phases despite the lower surface areas of the zirconia phase, but, more importantly, adsorption of hard Lewis bases can be used to control the chromatographic selectivity for cationic analytes on these zirconia-based stationary phases. In contrast to our prior work, here we show that when mixed-mode retention takes place, both retention and selectivity are easily adjusted by changing the type of hard Lewis base buffer anion, the type of buffer counter-ion (e.g., sodium, potassium, ammonium), the pH, and the ionic strength of the eluent as well as the type and amount of organic modifier.

Reversed-phase liquid chromatography with microspherical octadecyl-zirconia bonded stationary phases

Microspherical zirconia particles were synthesized and surface modified with octadecylsilane compounds for reversed-phase high performance liquid chromatography. Monomeric and “polymeric” octadecyl-zirconia bonded stationary phases were obtained by reacting the support with octadecyldimethylchlorosilane or octadecyltrichlorosilane, respectively. The surface coverage of the zirconia-based stationary phases with octadecyl functions was approximately the same as that of octadecyl-silica sorbents. These phases were evaluated in terms of reversed-phase chromatographic properties with non-polar, slightly polar and ionic species over a wide range of mobile phase composition and pH. Monomeric octadecyl-zirconia with end-capping exhibited some metallic interactions with both basic and acidic solutes, but these interactions were greatly reduced in the presence of competing agents ( e.g., tartrate ions) in the mobile phase. The “polymeric” octadecyl-zirconia sorbents exhibited higher retention than the monomeric ones with the various solutes investigated, and their residual adsoptivities toward acidic solutes were much lower. The retention of non-polar and slightly polar aromatic compounds was quasi-homoenergetic on both types of octadecyl-zirconia stationary phases. Stability studies conducted at extreme pH conditions (pH 2.0 and pH 12.0), have shown that “polymeric” octadecyl-zirconia sorbents are more stable than their monomeric counterparts. These stationary phases were quite useful in the separation of polycyclic aromatic hydrocarbons, alkylbenzene and phenyl alkylalcohol homologous series, oligosaccharides, dansyl-amino acids, peptides and proteins.