Determination of N-nitrosodimethylamine in Ranitidine Dosage Forms by ESI-LC-MS/MS; Applications for Routine Laboratory Testing

A practical high-performance liquid chromatography-mass spectrometry method was developed for the analysis of N-nitrosodimethylamine (NDMA) characterized as an impurity, in combination with reports of the carcinogen found in ranitidine samples. After simple extraction of ranitidine samples, all compounds were analyzed with a high-performance liquid chromatography-mass spectrometry. Sensitivity was enhanced by employing the ten-way valve switching technology, which was examined to allow NDMA to enter the mass spectrometry and cut out the ranitidine samples extremely. A good linear relationship was observed within 3-100 ng·mL(−1 )(r = 0.9992). The validated approach was effectively used to evaluate the NDMA contents in ranitidine samples in circulation, which revealed a difference among 21 batches. Quantitative determination of NDMA was within the scope of 3.38-57.05 ng·mL(-1). Moreover, the contamination levels of NDMA in seven batches of products from six manufacturers were listed to exceed the acceptable daily intake. The sensitive method was verified to be appropriate to determine NDMA, even with low contents of NDMA in ranitidine products; the analysis of the selected samples reveals that some samples exceeded the national limit requirements. Therefore, it is worthwhile to conduct comprehensive quality control of the other drugs containing NDMA.