Development and Validation of a RP-HPLC Method for Determination of Related Substances and Degradants in Entacapone

Dasari, Purnachand; Arava, Veera Reddy; Ramadevi, B.; Kameswarrao, Ch.V.S.L.; Madhusudhanreddy, Bethi

doi:10.1093/chromsci/bmw083

Cited by 4 publications

(7 citation statements)

References 11 publications

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“…Degradation of NTB due to oxidation is given in Figure 11 and oxidative degradation of NTB is also reported in the literature. 9 Thermal degradation There were no degradant peaks observed in thermal degradation indicating thermal stability of NTB and the % assay of the thermal degradation samples was found to be 98.22AE0.267. % RSD values and peak area were given in Table 3.…”

Section: Acid Degradationmentioning

confidence: 93%

“…5 Pasquini et al have reported a quality by design (QbD) based LC-MS method for estimating NTB and its impurities in soft gelatin capsules. 6 Several investigators have reported various methods like RP-UPLC, 7 LC-MS, 8 RP-HPLC in formulation, and determination of NTB and its stress degradation, 9 and which help in estimating the NTB. Some of the methods also reported degradation pathways and the degradation nature of NTB in various solvents with time.…”

Section: Introductionmentioning

confidence: 99%

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A stability indicating method development and validation of a rapid and sensitive RP-HPLC method for Nintedanib and its application in quantification of nanostructured lipid carriers

Velagacherla,

Nayak,

Bhaskar

et al. 2024

F1000Res

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Background Nintedanib (NTB) is a multiple tyrosine kinase inhibitor, been investigated for many disease conditions like idiopathic pulmonary fibrosis (IPF), systemic sclerosis interstitial lung disease (SSc-ILD) and non-small cell lung cancer (NSCLC). NTB is available as oral capsule formulation, but its ability to detect degradants formed through oxidative, photolytic and hydrolytic processes makes it difficult to quantify. In the current work, a novel reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated. Methods The developed method is simple, precise, reproducible, stable and accurate. The inherent stability of NTB was evaluated using the proposed analytical method approach and force degradation studies were carried out. NTB was separated chromatographically on the Shimadzu C18 column as stationary phase (250 ×4.6 mm, 5 µm) using an isocratic elution method with 0.1% v/v triethyl amine (TEA) in HPLC grade water and acetonitrile (ACN) in the ratio 35:65% v/v. The mobile phase was pumped at a constant flow rate of 1.0 ml/min, and the eluent was detected at 390 nm wavelength. Results NTB was eluted at 6.77±0.00 min of retention time (tR) with a correlation coefficient of 0.999, the developed method was linear in the concentration range of 0.5 µg/ml to 4.5 µg/ml. The recovery rate was found to be in the range of 99.391±0.468% for 1.5 µg/ml concentration. Six replicate standards were determined to have an % RSD of 0.04. Conclusion The formulation excipients didn’t interfere with the determination of NTB, demonstrating the specificity of the developed method. The proposed approach of the analytical method developed can be used to quantify the amount of NTB present in bulk drugs and pharmaceutical formulations.

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Section: Acid Degradationmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

A stability indicating method development and validation of a rapid and sensitive RP-HPLC method for Nintedanib and its application in quantification of nanostructured lipid carriers

Velagacherla,

Nayak,

Bhaskar

et al. 2024

F1000Res

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show abstract

Section: Introductionmentioning

confidence: 99%

“…These are the parameters that we have focused upon to produce a cost-effective and less time-consuming method. 9,10 The method is precise, rapid, simple and accurate to estimate NTB as per ICH Q2 (R1) guidelines. 8 The developed method is used to quantify NTB in Nanostructured lipid carriers (NLCs) loaded with NTB.…”

Section: Introductionmentioning

confidence: 99%

A stability indicating method development and validation of a rapid and sensitive RP-HPLC method for Nintedanib and its application in quantification of nanostructured lipid carriers

Velagacherla,

Nayak,

Bhaskar

et al. 2023

F1000Res

View full text Add to dashboard Cite

Background: Nintedanib (NTB) is a multiple tyrosine kinase inhibitor, been investigated for many disease conditions like idiopathic pulmonary fibrosis (IPF), systemic sclerosis interstitial lung disease (SSc-ILD) and non-small cell lung cancer (NSCLC). NTB is available as oral capsule formulation, but its ability to detect degradants formed through oxidative, photolytic and hydrolytic processes makes it difficult to quantify. In the current work, a novel reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated. Methods: The developed method is simple, precise, reproducible, stable and accurate. The inherent stability of NTB was evaluated using the proposed analytical method approach and force degradation studies were carried out. NTB was separated chromatographically on the Shimadzu C18 column as stationary phase (250 ×4.6 mm, 5 µm) using an isocratic elution method with 0.1% v/v triethyl amine (TEA) in HPLC grade water and acetonitrile (ACN) in the ratio 35:65% v/v. The mobile phase was pumped at a constant flow rate of 1.0 ml/min, and the eluent was detected at 390 nm wavelength. Results: NTB was eluted at 6.77±0.00 min of retention time (tR) with a correlation coefficient of 0.999, the developed method was linear in the concentration range of 0.5 µg/ml to 4.5 µg/ml. The recovery rate was found to be in the range of 99.391±0.468% for 1.5 µg/ml concentration. Six replicate standards were determined to have an % RSD of 0.04. Conclusion: The formulation excipients didn't interfere with the determination of NTB, demonstrating the specificity of the developed method. The proposed approach of the analytical method developed can be used to quantify the amount of NTB present in bulk drugs and pharmaceutical formulations.

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“…Sankar et al published a review article on the determination of tyrosine kinase inhibitors such as NTE, Dasatinib, Lapatinib, Imatinib, Sorafenib, Sunitinib, and Pazopanib [12]. HPLC [13][14][15] and HPTLC [16] methods were found and used to determine NTE from drug substances and drug products. Bio-analytical methods were published to estimate NTE from rat plasma [17] and human plasma [18,19].…”

mentioning

confidence: 99%

Development, stability‐indicating assessment, and evaluation of influential method conditions using a full factorial design for the determination of Nintedanib esylate‐related impurities

Yenda

Katari

Satheesh³

et al. 2023

J of Separation Science

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The design of an appropriate analytical method for assessing the quality of pharmaceuticals requires a deep understanding of science, and risk evaluation approaches are appreciated. The current study discusses how a related substance method was developed for Nintedanib esylate. The best possible separation between the critical peak pairs was achieved using an X-Select charged surface hybrid Phenyl Hexyl (150 × 4.6) mm, 3.5 μm column. A mixture of water, acetonitrile, and methanol in mobile phase-A (70:20:10) and mobile phase-B (20:70:10), with 0.1% trifluoroacetic acid and 0.05% formic acid in both eluents. The set flow rate, wavelength, and injection volumes were 1.0 ml/min, 285 nm, and 5 μl, respectively, with gradient elution. The method conditions were validated as per regulatory requirements and United States Pharmacopeia general chapter < 1225 >. The correlation coefficient for all impurities from the linearity experiment was found to be > 0.999. The % relative standard deviation from the precision experiments ranged from 0.4 to 3.6. The mean %recovery from the accuracy study ranged from 92.5 to 106.5. Demonstrated the power of the stabilityindicating method through degradation studies; the active drug component is more vulnerable to oxidation than other conditions. Final method conditions were further evaluated using a full-factorial design. The robust method conditions were identified using the graphical optimization from the design space.

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Development and Validation of a RP-HPLC Method for Determination of Related Substances and Degradants in Entacapone

Cited by 4 publications

References 11 publications

A stability indicating method development and validation of a rapid and sensitive RP-HPLC method for Nintedanib and its application in quantification of nanostructured lipid carriers

A stability indicating method development and validation of a rapid and sensitive RP-HPLC method for Nintedanib and its application in quantification of nanostructured lipid carriers

A stability indicating method development and validation of a rapid and sensitive RP-HPLC method for Nintedanib and its application in quantification of nanostructured lipid carriers

Development, stability‐indicating assessment, and evaluation of influential method conditions using a full factorial design for the determination of Nintedanib esylate‐related impurities

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