Development and validation of liquid chromatography method for determination of Ibrutinib in finished dosage forms using quality by design approach

Self Cite

A related-substances method was developed for the anticancer drug formulation apalutamide 60 mg tablets and validated using a liquid chromatography gradient elution method. All of the impurities and degradants were separated using the Luna Omega 5 μm Polar C 18 , (250 Â 4.6) mm HPLC column with a 1.0 ml min À1 flow rate.The detection was done at 225 nm by injecting the 10 μl of injection volume, controlling the sample temperature at 10 C and maintaining the column compartment temperature at 30 C. The total run time was 85 min. A 0.01 M disodium phosphate dihydrate pH 4.20 ± 0.05 buffer mixed with acetonitrile in the ratio of 73:27 (v/v) was used as mobile phase A. Mobile phase B consisted of water and acetonitrile in the ratio 30:70 (v/v). The proposed method was validated as per the current regulatory guidelines. The method precisions (RSD) at 100% specification level were 1.41, 1.74, 1.84, and 1.66% for the four impurities. The accuracy results were obtained between 96.0 and 106.3% for the limit of quantitation to the 150% level. The standard and sample solutions stability were established for 44 h at 10 C. The correlation coefficient (r) value was >0.999 for all four impurities, indicating good linearity between the concentration and peak response: 0.9999, 0.9999, 0.9999 and 1.0000. These results show the method's linearity. The three filter compatibility was proved and it was concluded that 0.45 μm Nylon, PTFE and PVDF filters are suitable. The robustness of the method was established by varying the conditions. The method specificity was proved and the forced degradation data reveal the method's stabilityindicating nature.

Section: Methodsmentioning

confidence: 99%

Development and validation of apalutamide‐related substances method in solid dosage forms using HPLC

Bandaru

Konduru

Kowtharapu

et al. 2023

Self Cite

“…QbD also designs a quality product that consistently delivers the intended performance. Similar principles and concepts have been adopted for analytical method development, termed ‘analytical QbD’ (Konduru et al, 2022; Kowtharapu et al, 2022; Liu et al, 2022; Subramanian et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

Development and validation of novel RP‐HPLC method for midostaurin determination using analytical quality by design approach from regulatory perspective and determination of major degradation compounds of midostaurin using LC–MS

Reddy

Konduru²,

Gundla

et al. 2022

Self Cite

Midostaurin (MTN), designated as an orphan medicinal product, is emerging as an important drug for treating acute myeloid leukemia and advanced systematic mastocytosis. The proposed method was developed and validated to evaluate the related impurities of MTN. The impurities were separated using a YMC Trait C18 ExRS column (150 Â 4.6 mm, 3 μm). Mobile phase A consisted of a 10-mM concentration of phosphate buffer adjusted to pH 3.0 with diluted orthophosphoric acid, and mobile phase B consisted of 90% acetonitrile and 10% water. The optimized chromatographic conditions were as follows: flow rate, 0.5 mL min À1 ; injection volume, 10 μL;UV detection, 290 nm; and linear gradient program, up to 65 min. The method was developed using an analytical quality by design approach. A systematic flow chart shows the evaluation, control, and life cycle management method. As part of method evaluation, risk assessment was conducted. The method has been validated per current guidelines of the International Conference on Harmonization. The recovery study and linearity ranges were established from the limit of quantification to 150% optimal concentrations. The recovery was found to be between 95.5 and 102.5%, and linearity (r 2 ) was 0.9998-0.9999 for all the identified impurities. The method precision results were achieved below 10% of relative standard deviation. Forced degradation studies were performed under chemical and physical stress conditions. The compound was sensitive to chemical stress conditions. During the study, the analyte degraded and was converted into the identified degradation impurities, and its molecular mass was found using the LC-MS technique.

“…An experimental design constructed according to Quality by Design (QbD) can identify the individual effects as well as interactions of the critical method variables, such as the organic ratio, the pH of the buffer or mobile phase, the flow rate, the column oven temperature and the gradient composition (Konduru et al, 2020; Konduru et al, 2022; Kowtharapu, Katari, Ch, et al, 2022; Kowtharapu, Katari, Sandoval, et al, 2022). The current method robustness was studied utilizing the QbD‐based Design of Experiments with Design Expert software.…”

Section: Introductionmentioning

confidence: 99%

Unique liquid chromatography technique for the determination of mirabegron in the presence of polymers; robustness by Design Expert in the light of Quality by Design

Konduru¹,

Kowtharapu

Gundla

2022

Self Cite

The current study is designed to estimate mirabegron in the presence of high molecular weight polymers using a unique liquid chromatography method and sample preparation technique. The proposed method is significant because of the many analytical issues faced during the development studies. Based on the experimental results, we finally achieved the stability-indicating power of the method. The adequately prepared mobile phase was in the ratio of pH 2.0 buffer and acetonitrile (80:20) v/v, and the buffer pH 2.0 was prepared as follows: 8.7 ml of perchloric acid, 2 ml of triethylamine and 3.0 g sodium hydroxide into 1 L of water mixed well. The system suitability parameters were achieved using a Waters X-Bridge C 18 (4.6 Â 150 mm, 3.5 μm) column and mobile phase. The optimized chromatographic conditions included a column temperature of 45 C, a flow rate of 1.0 ml min À1 ; an injection volume of 5 μl, UV 247 nm, and 15 min runtime. The method was validated and transferred to quality control as per International Conference on Harmonization Q2(R1) and the Chinese Pharmacopoeia 2020 edition <9101> and <9100>. The recovery and linearity results were obtained between 99.0 and 101.0%; the value of r 2 was 0.9998. The method robustness study was established by utilizing the Design of Experiments part of the Quality by Design concept. The method's stability-indicating nature was proved by a forced degradation study; all of the conditions for analyte peak purity were passed, and mass balance was achieved. The method was used to determine mirabegron assay, as well as content uniformity, blend uniformity and cleaning samples. It is a user-friendly and cost-effective method.