Determination of roxatidine in human plasma by liquid chromatography/electrospray mass spectrometry and application to a clinical pharmacokinetic study

Abstract

A rapid and sensitive liquid chromatography/mass spectrometry (LC/MS) method was developed and validated for the determination of roxatidine in human plasma. Roxatidine was extracted by single liquid-liquid extraction with tert-butyl methyl ether, and the chromatographic separation was performed on a C8 column. The total analytical run time was relatively short (5 min), and the limit of assay quantification was 2 ng/mL using 0.1 mL of human plasma. Roxatidine and the internal standard, propranolol, were monitored in selected ion monitoring (SIM) mode at m/z 307.3 and 260.3, respectively. The standard curve was linear over a concentration range from 2-500 ng/mL, and the correlation coefficients were >0.999. The mean intra- and inter-day assay accuracy ranged from 103.4-108.8% and 102.3-110.0%, respectively, and the mean intra- and inter-day precision was between 3.3-8.8% and 5.3-6.2%, respectively. The developed assay method was successfully applied to a pharmacokinetic study in human volunteers after oral administration of roxatidine acetate hydrochloride at a dose of 75 mg.

Quantification of roxatidine in human plasma by liquid chromatography electrospray ionization tandem mass spectrometry: Application to a bioequivalence study

“…E-mail address: ktlee@khu.ac.kr (K.-T. Lee). sensitivities [3][4][5][6]. Moreover, to the best of our knowledge, no liquid chromatography-tandem mass spectrometry (LC-MS/MS) based method has been previously described in the literature for the detection of roxatidine.…”

“…The latest assay using liquid chromatography-mass spectrometry (LC-MS) was reported [6]. However, these methods suffer from a number of disadvantages, e.g., they are time-consuming and require complex sample preparation [3], they need a large volume of plasma (≥0.1 mL) [4][5][6], have long run times (>4 min) [3][4][5][6], or have poor * Corresponding author. Tel.…”

“…The techniques adopted include gas chromatography-mass spectrometry (GC-MS) [3], high-performance liquid chromatography with an UV detector (HPLC-UVD) [4], and capillary gas chromatography with nitrogen selective detection [5]. The latest assay using liquid chromatography-mass spectrometry (LC-MS) was reported [6]. However, these methods suffer from a number of disadvantages, e.g., they are time-consuming and require complex sample preparation [3], they need a large volume of plasma (≥0.1 mL) [4][5][6], have long run times (>4 min) [3][4][5][6], or have poor * Corresponding author.…”

Determination of histamine H2 receptor antagonists in pharmaceutical formulations by CE-MS

“…14 Ranitidine (RAN), its metabolites and impurities in pharmaceutical preparations and urine were determined by LC-MS. [15][16][17][18][19][20] The same hyphenated technique was used to quantify famotidine (FAM) in plasma and urine. [21][22][23] Similar compounds such as roxatidine (ROX) and nizatidine (NIZ, as the internal standard) have also been determined by mass spectrometry. 24,25 Some methods allow the simultaneous separation of these compounds from others with similar properties.…”

Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Propranolol in Human Plasma and its Application to a Bioequivalence Study

“…[11] The LC-MS=MS method was also applied to quantify other drugs, using propranolol as internal standard, in clinical pharmacokinetic studies. [12,13] The aim of the present work was to develop and validate a simple, fast, precise, and accurate LC-MS=MS method, using liquid-liquid extraction, for the pharmacokinetic analysis of propranolol in human plasma supporting the bioequivalence study of two pharmaceutical formulations.…”