Quantitation of nitrofurantoin in human plasma by liquid chromatography tandem mass spectrometry

• Published in: Acta Pharmaceutica Vol. 63; no. 2; pp. 141 - 158
• Main Authors: Patel, Dinesh S., Sharma, Naveen, Patel, Mukesh C., Patel, Bhavin N., Shrivastav, Pranav S., Sanyal, Mallika
• Format: Journal Article Paper
• Language: English
• Published: Croatia De Gruyter Poland 01.06.2013; Hrvatsko farmaceutsko društvo
• Subjects: Adult; Anti-Infective Agents, Urinary - blood; Anti-Infective Agents, Urinary - chemistry; Anti-Infective Agents, Urinary - pharmacokinetics; bioequivalence; Capsules; Chromatography, Liquid - methods; Drug Monitoring - methods; human plasma; Humans; incurred sample reanalysis; LC-MS/MS; nitrofurantoin; Nitrofurantoin - blood; Nitrofurantoin - chemistry; Nitrofurantoin - pharmacokinetics; Nitrofurazone - blood; Nitrofurazone - chemistry; Nitrofurazone - pharmacokinetics; Reproducibility of Results; solid phase extraction; Solid Phase Extraction - methods; Tandem Mass Spectrometry - methods; Therapeutic Equivalency
• ISSN: 1330-0075; 1846-9558; 1846-9558
• DOI: 10.2478/acph-2013-0012

A reliable, selective and sensitive LC-MS/MS assay has been proposed for the determination of nitrofurantoin in human plasma. The analyte and nitrofurazone were extracted from 100 μL of human plasma via SPE on Strata-X 33 μm extraction cartridges. Chromatography was done on a BDS Hypersil C18 (100 mm × 4.6 mm, 5 μm) column under isocratic conditions. Quantitation was done using the multiple reaction monitoring (MRM) mode for deprotonated precursor to product ion transitions of nitrofurantoin (m/z 237.0 → 151.8) and nitrofurazone (m/z 197.0 → 123.9). The limit of detection and the lowest limit of quantitation of the method were 0.25 ng mL -1 and 5.00 ng mL -1 , respectively, with a linear dynamic range of 5.00-1500 ng mL -1 for nitrofurantoin. The intra- -batch and inter-batch precision (RSD, %) was ≤ 5.8 %, while the mean extraction recovery was > 92 %. The method was successfully applied to a bioequivalence study of a 100 mg nitrofurantoin capsule formulation in 36 healthy subjects.