Identification, Synthesis and Characterization of Novel Palbociclib Impurities

Nandyala Malyadri Reddy; K.R.S. Prasad; Ravi Sekhar Reddy Nandipati; Katam Reddy Vinod Kumar Reddy; Katam Reddy Vineela; G. Pavana Kumari; Naveen Mulakayala

doi:10.14233/ajchem.2025.33265

Issue

Vol. 37 No. 3 (2025): Vol 37 Issue 3, 2025

Issue Published : 28 February 2025

This work is licensed under a Creative Commons Attribution 4.0 International License.

Identification, Synthesis and Characterization of Novel Palbociclib Impurities

https://doi.org/10.14233/ajchem.2025.33265

Nandyala Malyadri Reddy

Department of Chemistry, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur-522302, India; SVAK Life Sciences, ALEAP Industrial Area, Hyderabad-500090, India

https://orcid.org/0000-0002-9462-5903

K.R.S. Prasad

Department of Chemistry, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur-522302, India

https://orcid.org/0000-0002-8087-954X

Ravi Sekhar Reddy Nandipati

SVAK Life Sciences, ALEAP Industrial Area, Hyderabad-500090, India

https://orcid.org/0000-0003-3317-0420

Katam Reddy Vinod Kumar Reddy

SVAK Life Sciences, ALEAP Industrial Area, Hyderabad-500090, India

https://orcid.org/0000-0001-8843-7677

Katam Reddy Vineela

Department of Periodontology, Indira Gandhi Institute of Dental Sciences, Sri Balaji Vidyapeeth, Pondicherry-607402, India

G. Pavana Kumari

Depatment of Chemistry, Sri Sathya Sai Institute of Higher Learning-Anantapur Campus Anantapur-515001, India

Naveen Mulakayala

SVAK Life Sciences, ALEAP Industrial Area, Hyderabad-500090, India

Corresponding Author(s) : Naveen Mulakayala

naveen071280@gmail.com

Asian Journal of Chemistry, Vol. 37 No. 3 (2025): Vol 37 Issue 3, 2025
Article Published : 28 February 2025

Abstract

Palbociclib is used for breast cancer treatment along with letrozole. Five major impurities were observed during the synthesis as well as in forced degradation studies, out of which, three impurities were identified during the penultimate step of palbociclib API synthesis. These three impurities were confirmed as palbociclib desacetyl impurity (PDA impurity), palbociclib desacetyl hydroxy impurity (PDH impurity) and palbociclib desacetyl hydroxyl methyl impurity (PDHM impurity). These impurities were formed due to the usage of palladium catalyst during the pre-final reaction between 1 and 2. The other two impurities were identified as N-oxides, which were formed due to the forced oxidative degradation studies of palbociclib. These two impurities were confirmed as palbociclib pyridine N-oxide and palbociclib piperazine N-oxide. All the five major impurities were identified, synthesized, characterized and confirmed by spectral analyses (¹H NMR, ¹³C NMR and mass spectra). These impurities were potentially important as reference standards for the R&D scientists working in process development and formulation development of palbociclib.

Keywords

Impurities Palbociclib Pyridine N-oxide Piperazine N-oxide

Reddy, N. M., Prasad, K., Nandipati, R. S. R., Reddy, K. R. V. K., Vineela, K. R., Kumari, G. P., & Mulakayala, N. (2025). Identification, Synthesis and Characterization of Novel Palbociclib Impurities. Asian Journal of Chemistry, 37(3), 698–706. https://doi.org/10.14233/ajchem.2025.33265

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J. McCain, P T., 40, 511 (2015).

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G. Vaddamanu, A. Goswami, R.S.R. Nandipati, Y.T. Malireddy, V.K.R. Katam Reddy and N. Mulakayala, ACS Omega, 8, 38494 (2023); https://doi.org/10.1021/acsomega.3c05325

Author biographies is not available.