QbD-Enabled Stability-Indicating Assay Method for the Estimation of Linezolid in Newly Developed Gelatin Nanoparticles for Anti-tubercular Therapy


The day-by-day increase in the novel drug delivery system market produces the utmost need to develop a reliable, robust, and accurate method. Moreover, the recent ICH (ICH Q8-Q11) guidelines recommend the use of modern systemic approaches such as quality by design (QbD) adopted for the development of robust analytical methods. Thus, the aim of the present study is to develop and validate a novel HPLC method for stability profiling after stress degradation studies of linezolid using QbD approach. The risk assessment matrix (RAM) and Taguchi orthogonal model were applied for screening of the most impacted CMAs/CMPs affecting the method performance. The 33 Box–Behnken design was employed to interpret the relationship between CMAs/CMPs and CAAs. The optimum chromatographic conditions were citrate-stabilized mobile phase methanol:water (50:50% v/v) at pH 4.0 ± 0.2 and flowrate of 1.0 mL min−1 with PDA detection at 251 nm. The stability-indicating capability of the method was verified by forced degradation studies. The method was found to be sensitive, specific, and linear in the concentration range between 5 and 30 µg mL−1 with a correlation coefficient (R2) of 0.9999. The method exhibits a high degree of accuracy, precision, and % recovery (between 99.77 and 101.2%) with LOD (0.053 µg mL−1) and LOQ (0.16 µg mL−1). The QbD-based stability-indicating method was successfully implemented for the detection of LNZ and its DPs in bulk and novel nanoparticulate dosage forms.

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We would like to thank the faculty members of SVKM’s NMIMS School of Pharmacy and Technology Management, Shirpur, India, for their support and encouragement throughout the research process.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Patil, K.D., Bagade, S.B. & Bonde, S.C. QbD-Enabled Stability-Indicating Assay Method for the Estimation of Linezolid in Newly Developed Gelatin Nanoparticles for Anti-tubercular Therapy. Chromatographia (2020). https://doi.org/10.1007/s10337-020-03925-9

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  • Linezolid
  • Analytical method development
  • Stability-indicating assay method
  • Forced degradation studies
  • Quality by design (QbD)