Buspirone, fexofenadine, and omeprazole: Quantification of probe drugs and their metabolites in human plasma

Abstract

Probe drugs are critical tools for the measurement of drug metabolism and transport activities in human subjects. Often several probe drugs are administered simultaneously in a —cocktail . This cocktail approach requires efficient analytical methods for the simultaneous quantitation of multiple analytes. We have developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three probe drugs and their metabolites in human plasma. The analytes include omeprazole and its metabolites omeprazole sulfone and 5-hydroxyomeprazole; buspirone and its metabolite 1-[2-pyrimidyl]-piperazine (1PP); and fexofenadine. These analytes and the internal standard lansoprazole were extracted from plasma using protein precipitation with acetonitrile. Gradient reverse-phase chromatography was performed with 7.5 mM ammonium bicarbonate and acetonitrile, and the analytes were quantified in positive ion electrospray mode with multiple reaction monitoring. The method was validated to quantify the concentration ranges of 1.0–1000 ng/ml for omeprazole, omeprazole sulfone, 5-hydroxyomeprazole, and fexofenadine; 0.1-100 ng/ml for buspirone, and 1.0-100 ng/ml for 1PP. These linear ranges span the plasma concentrations for all of the analytes from probe drug studies. The intra-day precision was between 2.1 –16.1%, and the accuracy ranged from 86 -115% for all analytes. Inter-day precision and accuracy ranged from 0.3 – 14% and from 90 – 110%, respectively. The lower limits of quantification were 0.1 ng/ml for buspirone and 1 ng/ml for all other analytes. This method provides a fast, sensitive, and selective analytical tool for quantification of the six analytes in plasma necessary to support the use of this probe drug cocktail in clinical studies.

Nanomaterial-based electrochemical sensing of neurological drugs and neurotransmitters

“…BUS is a probe drug that is often administered along with fexofenadine and omeprazole. There is one HPLC method to detect them simultaneously [ 146 ]. A voltammetric method for simultaneous determination of BUS, fexofenadine and omneprazone is needed since, if selective, it will have the advantage of no need for prior sample preparation steps.…”

The effect of apatinib on pharmacokinetic profile of buspirone both in vivo and in vitro

“…CYP3A4 is responsible for the metabolism of buspirone generating 2 major metabolites. [20] The metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) is formed via N-dealkylation, and another metabolite 6-hydroxybuspirone (6-OH buspirone) is formed via hydroxylation. [14,21,22] 1-PP has similar pharmacological activity as buspirone, and 6-OH buspirone may be beneficial to treat anxiety disorder.…”

Development of a Highly Sensitive Methodology for Quantitative Determination of Fexofenadine in a Microdose Study by Multiple Injection Method Using Ultra-High Performance Liquid Chromatography with Tandem Mass Spectrometry

“…Previous studies have frequently used the protein precipitation method using an organic solvent for sample treatment and the LLOQs in the "ng/mL" range to determine the concentration of fexofenadine in biological samples by LC-MS/MS. [7][8][9][10][11][12][13][14] However, the drug concentration of samples in a microdose study cannot be measured at an LLOQ of only ng/mL because of lack of sensitivity. 5,6,[15][16][17][18][19][20] In case of employing SPE or liquid-liquid extraction for sample preparation, it is possible to set the LLOQ at pg/mL, but total sample analysis is required, which demands increased time as the procedure of sample preparation is quite complex.…”