QbD‐based stability‐indicating liquid chromatography (RP‐HPLC) method for the determination of flurbiprofen in cataplasm

Abstract

A nonsteroidal drug called flurbiprofen (FBN) has analgesic, anti‐inflammatory and antipyretic activity. Currently the determination of FBN in cataplasm does not have any pharmacopeial method. However, the drug substance, tablet and ophthalmic solution formulations do have pharmacopeial methods. The development and validation of an accurate, precise and stability‐indicating analytical method for the determination of FBN in cataplasm formulations is reported. The gradient method was employed for the quantification of FBN in the presence of internal standards such as biphenyl. A nonpolar separation phase (C18, 250 × 4.6 mm, 5 μm Inertsil column; GL Sciences) was used. The optimal flow rate, column oven temperature, injection volume and detector wavelengths were 1.0 ml/min, 40°C, 20 μl and 245 nm, respectively. Mobile phase A was a mixture of water and glacial acetic acid (30:1 v/v) pH adjusted to 2.20 with glacial acetic acid or 1 m NaOH; mobile phase B was methanol (100%). The gradient elution program was [time (min)/% B]: 5/60, 20/70, 25/70, 30/60 and 40/60. The obtained RSDs for the precision and intermediate precision were 0.7 and 0.5%. The percentage recovery ranged from 99.2 to 100.4%. The linear regression coefficient >0.9996 indicates that all peak responses were linear with the concentration. The sample and standard solutions were stable for up to 24 h on the benchtop and in the refrigerator. The critical peaks were well separated from the generated peaks owing to forced degradation, including diluent and placebo peaks. The method validation data and quality by design‐based robustness study results indicate that the developed method is robust and fit for routine use in the quality control laboratory. The proposed method is specific, accurate and precise, and the quality by design utilized the first method for the determination of FBN in cataplasm formulations. Transdermal patches and gels have low extraction capacity and this method is applicable for quantification.

Quality by design tool–evaluated stability‐indicating ultra‐performance liquid chromatography method for the determination of drugs (ritonavir and darunavir) used to treat the human immunodeficiency virus/acquired immunodeficiency syndrome

“…The parameters evaluated during the current method development were specificity, linearity, range, accuracy, robustness, and precision. The proposed method was validated using the International Conference on Harmonization (ICH) Q2 (R1) guidelines (International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use, 2005; Kowtharapu et al, 2023; Muchakayala et al, 2021; Naresh & Madhuri, 2014; Nathi et al, 2023; Reddy Saddala et al, 2022; Satyanarayana et al, 2011; USP 43 NF 38 General Chapters: <1225>, 2020a; USP 43 NF 38 General Chapters: <621>, 2020b).…”

Valbenazine isomers and enantiomer determination by chiral normal phase liquid chromatography

“…The injection volume was 10 μl, and detection was performed on 282 nM using PDA (photodiode array) detector. Valbenazine and its isomers and enantiomer were separated with the abovementioned condition, and the method was validated as per the International Council of Harmonization (ICH) guidelines 25–39 . The proposed method has been validated in terms of specificity, limit of detection (LOD), limit of quantification (LOQ), precision, linearity and range, accuracy, and robustness.…”

“…Valbenazine and its isomers and enantiomer were separated with the abovementioned condition, and the method was validated as per the International Council of Harmonization (ICH) guidelines. [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] The proposed method has been validated in terms of specificity, limit of detection (LOD), limit of quantification (LOQ), precision, linearity and range, accuracy, and robustness. The accuracy is expressed regarding % recovery by adding known impurities in the sample solution.…”

Determination of Valbenazine related substances by liquid chromatography method complying with the current regulatory guidelines. Method robustness evaluation by Design of Experiments software

“…A Quality by Design (QbD)‐based Design of Experiments (DoE) helps you understand the importance of critical process parameters [11–17]. Evaluate viable and robust method conditions using multivariate DoE.…”

“…The object of this study is to develop a stability indicating simple, sensitive, precise, reliable, and accurate RP-HPLC method with UV detection for the determination of Valbenazine and its impurities. A Quality by Design (QbD)-based Design of Experiments (DoE) helps you understand the importance of critical process parameters [11][12][13][14][15][16][17]. Evaluate viable and robust method conditions using multivariate DoE.…”