An ultra high performance liquid chromatography-orbitrap high resolution mass spectrometry(UHPLC-Orbitrap HRMS) was used for the determination of N-nitrosodimethylamine(NDMA) in famotidine and its preparations.The samples were extracted with methanol

followed by vortex mixing

constant temperature shaking

high speed centrifugation and microfiltration

and finally analyzed by liquid chromatography-mass spectrometry(LC-MS).The chromatographic separation was performed on an ACE EXCEL 3 C18-AR(150 mm×4.6 mm

3 μm) column at 30 ℃ by gradient elution

with water and acetonitrile both contained 0.1% formic acid as mobile phases at a flow rate of 0.50 mL/min.The temperature of the autosampler was set at 4 ℃

and the mass spectrometer was protected with a valve switching apparatus.The MS analysis was performed with ESI ion source in positive ion parallel reaction monitoring(PRM) scanning mode

and the quantitation was achieved by the external standard method.Results showed that there was a good linear relationships for NDMA in the concentration range of 1.00-100.00 ng/mL with correlation coefficient(r) of 0.999 7.The limit of detection and limit of quantitation were 0.20 ng/mL and 1.00 ng/mL

respectively.The mean recoveries of NDMA from spiked famotidine and its preparations ranged from 98.5% to 108% with relative standard deviations(RSD) of 2.3%-6.7%.The method was then applied to the determination of NDMA in famotidine and its preparations.Among 47 batches of samples

NDMA was detected in 1 batch of famotidine and 2 batches of famotidine preparations

which contents exceeded the limit requirement.This method is sensitive

accurate and easy to operate

and could be used for the determination of NDMA in famotidine and its preparations.