Indian Journal of Pharmaceutical Education and Research logo
Submit
Indian Journal of Pharmaceutical Education and ResearchAn Official Publication of Association of Pharmaceutical Teachers of India (APTI)
Article

A Validated LC-MS/MS Method for Determination at Trace Level of Nitrosamine Impurities in Doxofylline API

1,2, 1, 1

  1. 1Department of Pharmaceutical Analysis, KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur.
  2. 2Department of Pharmaceutical Analysis, Sarojini Naidu Vanita Pharmacy Maha Vidyalaya, Tarnaka, Secunderabad, Telangana, INDIA.

CORRESPONDENCE

Guntupalli Chakravarthi

Department of Pharmaceutical Analysis, KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur.

Chakra_varthi123@kluniversity.in

Received: 14-07-2023; Accepted: 10-10-2024.

Volume 58, Issue 4s (Supplement) · pp. s1262-s1270 · 2024 · DOI: 10.5530/ijper.58.4s.121

ABSTRACT

Background: The FDA looked at popular amine-based API synthesis processes and found that these processes might additionally introduce nitrosamine-hazardous substances. The current method describes trace-level quantification of Nitrosamine impurities (NDEA, NDIPA, NDIPA, NEIPA, NMPA, NDBA, NDMA and NMBA) in the Doxofylline API.Materials and Methods: With the help of Waters® ACQUITY® UPLC BEH C18 (150x4.6 mm, 5 μm) and a 0.8 mL/min flow, a gradient programme (0.1%v/v formic acid and methanol) continuing for 14 min was used to achieve separation. Using Multiple Reaction Monitoring (MRM), all nitrosamine impurities were ionized and measured in the positive polarity mode of APCI.Results: Protonated molecular ions (M+H)+ were acquainted at: m/z 75 (parent), m/z 58 (product), m/z 103 (parent), m/z 47 (product), m/z 131 (parent), m/z 89 (product), m/z 117.1 (parent), m/z 74.8 (product), m/z 147.1 (parent), m/z 117 (product), m/z 137 (parent), m/z 66 (product), m/z 159 (parent), m/z 103 (product), m/z 267.2 (parent), m/z 181.1 (product), respectively, for NDMA, NDEA, NDIPA, NEIPA, NMBA, NMPA, NDBA and Doxofylline, with their retention times observed as 4.04, 6.83, 8.97, 7.98, 4.92, 9.25, 11.06 and 7.15 min, respectively.Conclusion: The coefficient of determination (r2) for individual impurities was found to be between 0.996 and 1.000. S/N method was used to establish limits of detection and quantification, which turned out as 0.0040 μg/mL-0.0174 μg/mL and 0.0060 μg/mL-0.0262 μg/mL, respectively. Each of the validation parameters falls within the allowed ranges as per USP.

KEYWORDS

Open in new tab

REFERENCES

As published

Showing references and in-text citations exactly as published.

    Cite this article

    SELECT FORMAT

    Remidicherla, S. S., Chakravarthi, G., & Malothu, N. (2024). A Validated LC-MS/MS Method for Determination at Trace Level of Nitrosamine Impurities in Doxofylline API. Indian Journal of Pharmaceutical Education and Research, 58(4s), s1262-s1270. https://doi.org/10.5530/ijper.58.4s.121

    Copyright and licence

    © 2024 Author(s)

    This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. CC BY 4.0