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An Application of Quality by Design and Analytical Greenness Assessment Approach for the Development of Erlotinib Stability Indicating Method

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Abstract

Pharmaceutical regulators are worried about medication quality and stability since drug degradation may result in harmful chemicals. Erlotinib (ERL) is a tyrosine kinase inhibitor associated with the epidermal growth factor receptor (EGFR) containing susceptible functional groups such as quinazoline and amine ketone, methoxy, and ethoxy leads to a reduction in pharmaceutical quality. According to the ICH-Q1A (R2) guideline, the goal of ERL stability studies is to establish its susceptibility to degradation under various environmental conditions. A novel isocratic stability–indicating liquid chromatography method has been developed using systemic quality by design (QbD) approach. The QbD strategy includes screening and optimization as phases. Placket Burman was used for primary parameters screening, and critical factors were optimized with response surface design. The prepared degradation samples (acid, base, neutral hydrolysis, oxidative, photolytic, and thermal) were separated using a Shimadzu GIST C18 column (250 mm × 4.6 mm, 5 µm) with 15 mM ammonium formate: ACN (58:42% v/v) as mobile phase, 0.9 mL/min flow rate, and 246 nm wavelength, which was found to be LC–MS compatible. A total of six degradation products (DPs) were identified with the optimized chromatography method. The drug was sensitive toward acidic and basic hydrolysis, but it remained stable under neutral, oxidative, thermal, and photolytic stress conditions. The optimized method was sensitive, specific, and robust, with linearity ranging from 10 to 35 µg/mL, with a correlation coefficient (R2 = 0.9997). The analytical method greenness score was calculated and observed that the developed method is green.

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All the data generated or analyzed during this study are included in this published article and in form of supplementary data.

Abbreviations

nm:

Nanometer

ppm:

Parts per million

°C:

Degree Celsius

mL:

Milliliter

µg:

Micron gram

SIAM:

Stability indicating assay method

mg:

Milligram

Conc.:

Concentration

HPLC:

High performance liquid chromatography

LC/MS–MS:

Liquid Chromatography Mass Spectrometry

HCl:

Hydrochloric acid

NaOH:

Sodium hydroxide

MeOH:

Methanol

ACN:

Acetonitrile

pH:

Potential of hydrogen

Hrs:

Hours

min:

Minute

DOE:

Design of experiment

QbD:

Quality by design

ERL:

Erlotinib

H2O2 :

Hydrogen peroxide

PBD:

Plackett Burman design

CCD:

Central composite design

RSD:

Response surface design

ANOVA:

Analysis of variance

LOD:

Limit of detection

LOQ:

Limit of quantification

ICH:

International Council for Harmonization

DPs:

Degradation products

CQAs:

Critical quality attributes

CAAs:

Critical analytical attributes

AMGS:

Analytical method greenness score

CMAs:

Critical material attributes

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  1. Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKMs NMIMS, V. L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra, 400056, India

    Satyam Gundecha, Mital Patel & Y. C. Mayur

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Gundecha, S., Patel, M. & Mayur, Y.C. An Application of Quality by Design and Analytical Greenness Assessment Approach for the Development of Erlotinib Stability Indicating Method. Chromatographia 85, 575–588 (2022). https://doi.org/10.1007/s10337-022-04167-7

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