Determination of famotidine in low‐volume human plasma by normal‐phase liquid chromatography/tandem mass spectrometry

Abstract

A rapid, sensitive and robust assay procedure using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) for the determination of famotidine in human plasma and urine is described. Famotidine and the internal standard were isolated from plasma samples by cation-exchange solid-phase extraction with benzenesulfonic acid (SCX) cartridges. The urine assay used direct injection of a diluted urine sample. The chromatographic separation was accomplished by using a BDS Hypersil silica column with a mobile phase of acetonitrile-water containing trifluoroacetic acid. The MS/MS detection of the analytes was set in the positive ionization mode using electrospray ionization for sample introduction. The analyte and internal standard precursor-product ion combinations were monitored in the multiple-reaction monitoring mode. Assay calibration curves were linear in the concentration range 0.5--500 ng ml(-1) and 0.05--50 microg ml(-1) in plasma and urine, respectively. For the plasma assay, a 100 microl sample aliquot was subjected to extraction. To perform the urine assay, a 50 microl sample aliquot was used. The intra-day relative standard deviations at all concentration levels were <10%. The inter-day consistency was assessed by running quality control samples during each daily run. The limit of quantification was 0.5 ng ml(-1) in plasma and 0.05 microg ml(-1) in urine. The methods were utilized to support clinical pharmacokinetic studies in infants aged 0-12 months.

A single LC–tandem mass spectrometry method for the simultaneous determination of four H2 antagonists in human plasma

“…Although HPLC method is mature and relatively economical, limitations such as sensitivity, selectivity and throughput were often encountered during the method development. Only several studies employed LC-MS or LC-MS/MS method [8,17,24,25,28,29]. Xu et al [8] published an HPLC-APCI-MS/MS method for the quantification of cimetidine.…”

“…These methods both showed broad linearity and high sensitivity. Campanero et al [24] and Zhong et al [25] reported LC-MS and LC-MS/MS methods, respectively, for the determination of famotidine in human plasma. Wu et al [28], as well as Chen et al [29] developed LC-MS methods for the determination of lafutidine.…”

“…Sample preparation involved protein precipitation, liquid-liquid extraction (LLE), and solidphase extraction (SPE). However, limitations of these LC-MS and LC-MS/MS methods include use of structure analogue as internal standard which is commercial unavailable [25]; utilization of large volumes of plasma, usually more than 200 L [24,28]; long run time was needed because of gradient elution [>10 min] [8]; relatively high lower limit of quantification (LLOQ), and/or the relatively narrow dynamic range of the calibration curve [24,28]. Furthermore, these LC-MS and LC-MS/MS methods are only available for analyzing one of the four H 2 antagonists.…”

“…A number of analytical methods have been reported for the determination of individual H 2 antagonists in human plasma since 1990 years, cimetidine [1][2][3][4][5][6][7][8], ranitidine [9][10][11][12][13][14][15][16][17], famotidine [18][19][20][21][22][23][24][25], and lafutidine [26][27][28][29]. Apart from some uncommonly used methods such as free capillary zone electrophoresis [4], micellar electrokinetic capillary chromatography [7], HPTLC [13], most reports utilized HPLC-UV method [1][2][3][4][5][6][7][9][10][11][12][13][14][15][16][18][19]…”

Development and Validation of Spectrophotometric and Pre-column Derivatization HPLC Method for Determination of Famotidine in Pharmaceuticals by Reaction with Sodium Nitroprusside; Application to Combined Tablets

“…FMT is a histamine H 2 -antagonist, usually administred for gastric, duodenal ulceration and gastro-esophageal reflux disease [2]. Different methods were used for the quantification of FMT in its dosage forms and biological fluids like: spectrophotometry [3][4][5][6][7][8][9] spectrofluorimetry [10,11], voltammetry [12,13], TLC [14,15], HPLC [16][17][18][19][20][21][22][23][24][25] and capillary electrophoresis [16,[26][27][28]. U.S.P.…”