We are developing a test for N-nitroso cinacalcet with MDD of 396.7mg/day and AI=400ng/day, so the limit is set as 1.0ppm
Due to the presence of trifluoromethyl in the structure, the LC-MS response is very low (there may be ion inhibition), and the HPLC-UV method is found to have impurity interference (the specificity is not very good).
Anyone have a suitable detection method to recommend?
You will have to optimize the impurity response on LCMS itself. HPLC is unreliable at this level of quantitation.
We have developed methods on HRMS as well as QQQ for both the API and FP
Hola estimado. Nosotros hemos desarrollado metodologías para la detección y cuantificación en diversos N-nitroso´s por LC-MS/MS. Cabe mencionar que una de las partes mas importantes para obtener un método sensible y especifico es la separación cromatografíca de los N-nitroso´s del ingrediente activo API, ya que puede causar supresión iónica. Recomiendo la fuente de ionización por Atmospheric pressure chemical ionization (APCI) y el modo del detector en Multiple reaction monitoring (MRM). Si cuentas con el estándar, podrías colocar el analizador en modo Product Ion para obtener las transiciones.
Saludos. Seguimos en comunicación.
Does N-nitroso-cinacalcet exhibit tautomerism? Our LC-UV analysis reveals two distinct peaks in an 80:20 ratio. Both share the same m/z of 387 on LC-MS-MS. Could these represent tautomeric forms, or might one correspond to a hydrazine-related analog?
Hello, I developed a method for N-nitroso cinacalcet by LC-MS/MS, MRM mode, and had no problems with sensitivity. We were able to detect even less than 0.1 ppm. In fact, I had to use a matrix quantification method due to the matrix effect. And we also observed two peaks for this nitrosamine, the second peak being the n-nitroso S-isomer.
N-Nitroso Cinacalcet can exist as a syn and anti mixture. Therefore two peaks are possible and might resemble a peak with tailing.