The Sensitive Lc-Msms Method & Validation Procedure To Determination Of The N-Nitroso Isavuconazonium

Abstract

Background and purpose: The Isavuconazonium sulfate is the Active pharmaceutical ingredient (API) which is used for treatment for the Fungal infections, N-Nitroso Isavuconazonium sulfate(NNIS)   is the Nitroso drug substance related impurity (NDSRI) can cause the cancer even the presence of very minute level in the API, thus the determination technique is required to know the amount of impurity is present in the pharmaceutical product which may form during the manufacturing process of the API. The trace level determination of this impurity is difficult due the similar structure of the Impurity as well as API except Nitroso group. We have developed method it explains the ppb level determination of  N-Nitroso Isavuconazonium sulfate in Isavuconazonium sulfate drug substance by LC-MSMS with suitable precision ,accuracy,  LOD (Limit of Detection ) & LOQ (Limit of Quantification), Solution stability by using Sciex-4500 (Q-trap ) LC-MSMS instrument. Experimental approach: The Required separations were achieved in a Kinetix® F5 100A°(Part No: OOF-4723-EO) HPLC Column with 150mm *4.6mm and 2.6µm . The LC-MS system operated flow rate of 0.5 mL/min for 20 minutes. When determining the N-Nitrosamine Isavuconazonium sulfate impurity (NNIS) of commercially manufactured batches of Isavuconazonium sulfate drug substances, this established approach may be helpful for identification and quantification of N-Nitrasamine impurity. Key results: The specification limit for This N-Nitroso isavuconazonium sulfate impurity (NNIS) is 48ppb, the developed method is capable to detect from 1.32ppb (LOD) & able to Quantify from 4.0ppb(LOQ) Conclusion: The well-known LCMS technique was developed to be Precise, selective, accurate & Specific.