Quantitative determination of famotidine in human maternal plasma, umbilical cord plasma and urine using high‐performance liquid chromatography–mass spectrometry

Abstract

The liquid chromatography with electrospray ionization mass spectrometry for the quantitative determination of famotidine in human urine, maternal and umbilical cord plasma was developed and validated. The plasma samples were alkalized with ammonium hydroxide and extracted twice with ethyl acetate. The extraction recovery of famotidine in maternal and umbilical cord plasma ranged from 53% to 64% and 72% to 79%, respectively. Urine samples were directly diluted with the initial mobile phase then injected into the HPLC system. Chromatographic separation of famotidine was achieved by using a Phenomenex Synergi™ Hydro-RP™ column with a gradient elution of acetonitrile and 10 mM ammonium acetate aqueous solution (pH 8.3, adjusted with ammonium hydroxide). Mass Spectrometric detection of famotidine was set in the positive mode and used a selected ion monitoring method. Carbon-13-labeled famotidine was used as internal standard. The calibration curves were linear (r2> 0.99) in the concentration ranges of 0.631-252 ng/mL for umbilical and maternal plasma samples, and of 0.075-30.0 μg/mL for urine samples. The relative deviation of method was less than 14% for intra- and inter-day assays, and the accuracy ranged between 93% and 110%. The matrix effect of famotidine in human urine, maternal and umbilical cord plasma is less than 17%.

Use of a monolithic column for the development and validation of a HPLC method for the determination of famotidine, cimetidine and nizatidine in biological fluids

“…A literature survey retrieved a large number of references reporting analytical methods for the determination of these compounds. Mainly separation techniques such as Gas Chromatography (GC) [2], High Performance Thin Layer Chromatography (HPTLC) [3][4][5][6][7][8][9][10], Capillary Electrophoresis (CE) [11][12][13][14][15][16][17] and High Performance Liquid Chromatography (HPLC) [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] have been used, with the latter being the predominant technique for the determination of these compounds in a variety of matrices, utilizing different methods of sample pretreatment and detection modes. HPLC with ultra-violet (UV) detection, employing reversed phase particle packed columns, is most frequently used for the analysis of these drugs in pharmaceutical preparations and biological fluids.…”

Do we have an understanding on incurred sample analyses – introspection?

“…A recently published article in Biomedical Chromatography described a complete validation of famotidine in number of matrices (Wang et al ., ). Interestingly, the matrix effect determination in this work featured evaluation of famotidine in both maternal plasma and umbilical cord plasma (Wang et al ., ).…”

“…A recently published article in Biomedical Chromatography described a complete validation of famotidine in number of matrices (Wang et al ., ). Interestingly, the matrix effect determination in this work featured evaluation of famotidine in both maternal plasma and umbilical cord plasma (Wang et al ., ). While it appeared that there may be marginal interference in umbilical cord plasma as compared with maternal plasma, this had no or negligible consequences for the accuracy and precision of the assay (Wang et al ., ).…”

“…Interestingly, the matrix effect determination in this work featured evaluation of famotidine in both maternal plasma and umbilical cord plasma (Wang et al ., ). While it appeared that there may be marginal interference in umbilical cord plasma as compared with maternal plasma, this had no or negligible consequences for the accuracy and precision of the assay (Wang et al ., ). However, it raised an important question in my mind, on how to tackle incurred sample reanalysis (ISR) in such situations.…”