Comparison of hydrophilic interaction and reversed‐phase liquid chromatography coupled with tandem mass spectrometric detection for the determination of three pharmaceuticals in human plasma

Abstract

In the present study, hydrophilic interaction liquid chromatography (HILIC) and reversed-phase liquid chromatography (RPLC) combined with tandem mass spectrometric detection (MS/MS) were evaluated and compared for the determination of donepezil, cetirizine and loratadine in human plasma, in terms of sensitivity and sample preparation procedure. A retention study for the above compounds of various polarities was performed, using both C(18) and silica columns, with several aqueous-organic mobile phase ratios, in order to investigate their retention mechanism profile under HILIC and RPLC. Both chromatographic conditions were compared for chromatographic analysis of plasma samples processed with a liquid-liquid extraction (LLE) method for donepezil determination, resulting in significantly higher sensitivity under HILIC. Furthermore, HILIC and RPLC were compared for direct injection, and novel methods including LLE, solid-phase extraction and protein precipitation protocols were developed. Direct injection technique significantly reduced sample preparation time, increasing at the same time method sensitivity. The current study contributes to broadening the range of analyzable compounds by HILIC-MS/MS to molecules of medium polarity.

A Sensitive Precolumn Derivatization Method for Determination of Piperazine in Vortioxetine Hydrobromide Using a C8 Column and High-Performance Liquid Chromatography–Mass Spectrometry

“…HILIC has been widely used for the analysis of polar compounds, including sugars, natural products, and drugs. [19][20][21][22][23][24] However, the solubility of polar compounds is limited in the high concentration organic solvents typically used in the initial mobile phase of HILIC. Furthermore, the mixed-mode bonded column life deteriorates rapidly due to its high attrition rate of packing.…”

Enantioselective determination of cetirizine in human plasma by normal-phase liquid chromatography–atmospheric pressure chemical ionization–tandem mass spectrometry

“…Due to the polarity of cetirizine, which makes it difficult to retain on reversed-phase columns using a mobile phase with a high percentage of organic solvent, hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) methods [34,38,40] were developed and applied to quantify cetirizine in human plasma. When operated under higher organic content in the mobile phase, HILIC columns showed good retention and peak shape of polar analytes.…”

“…However, these methods have a number of disadvantages; for example, they require a large volume of sample (≥1.0 mL), and have long run time, low separation resolution, and poor sensitivity. More recently, liquid chromatography-mass spectrometry (LC-MS) [30][31][32] and tandem mass spectrometry (LC-MS/MS) [33][34][35][36][37][38][39][40][41][42][43] have been used to determine cetirizine in a biological matrix because of their high sensitivity and specificity.…”

Emerging Analytical Separation Techniques with High Throughput Potential for Pharmaceutical Analysis, Part II: Novel Chromatographic Modes

“…Many pharmaceutical compounds and/or their metabolites were determined in human plasma, e.g. atenolol [6], cetirizine [7,12], omeprazole and its main active metabolite 5-OH omeprazole [8], muraglitazar [9], the glucuroconjugate metabolites from the anaesthetic drug propofol [10], donepezil [12], loratadine [12], isoniazid [14], dacarbazine and its metabolite 5-amino-4-imidazolecarboxamide [15], and gaboxadol [17]. In both human plasma and cerebrospinal fluid, miglustat was analyzed [13].…”

“…HILIC methods were developed to be applied during drug monitoring, pharmacokinetic and drug-drug interaction studies [6][7][8][9][10][11][12][13][14][15][16][17]. Many pharmaceutical compounds and/or their metabolites were determined in human plasma, e.g.…”