Quantification and In Silico Toxicity Assessment of Tazarotene and its Impurities for a Quality and Safe Drug Product Development

2019 ◽  
Vol 57 (7) ◽  
pp. 625-635 ◽  
Author(s):  
NVVSS Narayana Murty Nagulakonda ◽  
Ravi Shekar Ananthula ◽  
T Krishnamurthy ◽  
Muguda Ravi Prasada Rao ◽  
Gollapalli Nageswara Rao
Keyword(s):  
Product Development ◽  
In Silico ◽  
Limit Of Detection ◽  
Drug Product ◽  
Acne Vulgaris ◽  
Toxicity Assessment ◽  
Limit Of Quantification ◽  
Related Substances ◽  
In Silico Toxicity

Abstract Tazarotene is internationally accepted common name for ethyl 6-[(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate. It is a synthetic retinoid used for the topical treatment of mild to moderate plaque psoriasis, acne vulgaris and photo aging. To ensure the quality of drug product and drug substance, a LC–MS compatible UHPLC method was developed for quantification of drug and its related substances. Stationary phase with fused core particle technology is used for the separation of impurities. Limit of quantification and limit of detection of the method are 0.1 and 0.03%, respectively. Precision of the method for Tazarotene and all its related substances is less than 2.2% RSD. The correlation coefficient is >0.999. Accuracy of method is ranged from 95.3% to 107.0%. Application of this method in stability analysis has been demonstrated by analyzing stressed samples. Experimental design is used for the verification of robustness of the method. To ensure the safety, an in silico toxicity of the drug and its related substances were determined using TOPKAT and DEREK toxicity predictions Both UHPLC and in silico methods were validated as per the ICH Q2 and ICH M7 guidelines, which will enable a rapid product development of Tazarotene topical formulations while ensuring the safety and quality of product.

scholarly journals Quantification and In Silico Toxicity Assessment of Nimesulide and its Related Substances

2017 ◽  
Vol 55 (5) ◽  
pp. 508-517
Author(s):  
NVVSS Narayana Murty Nagulakonda ◽  
Ravi Shekar Ananthula ◽  
Krishna Phani Chandra Susarla ◽  
T. Krishnamurthy ◽  
Nageswara Rao Gollapalli
Keyword(s):  
In Silico ◽  
Toxicity Assessment ◽  
Related Substances ◽  
In Silico Toxicity

scholarly journals Application of RP-HPLC for the Estimation of Allopurinol and Its Related Substances in Bulk and Tablet Dosage Form

2021 ◽  
pp. 11-20
Author(s):  
Ch. Jaswanth Kumar ◽  
Prachet Pinnamaneni ◽  
Siva Prasad Morla ◽  
K. N. Rajini Kanth ◽  
Rama Rao Nadendla
Keyword(s):  
Drug Testing ◽  
Dosage Form ◽  
Method Development ◽  
Limit Of Detection ◽  
Limit Of Quantification ◽  
Related Substance ◽  
Related Substances ◽  
Rp Hplc ◽  
Relative Standard ◽  
Tablet Dosage

Aims: The main aim of the present study was to develop and validate a simple and cost- effective method for the estimation of allopurinol and its related substances by using RP-HPLC. Study Design:  Estimation of Allopurinol and its related substance in bulk and tablet dosage forms by RP-HPLC. Place and Duration of Study: Chalapathi Drug Testing Laboratory, Chalapathi Institute of Pharmaceutical Sciences, Chalapathi Nagar, Lam, Guntur-522034 between October 2020 to January 2021. Methodology: Method development was carried out by using Schimadzu, Prominence-i series LC 3D-Plus autosampler embedded with lab solutions software, equipped with PDA detector using YMC column (150 mm X 4.6 mm, 3 μm) and 0.1M Ammonium acetate buffer as a mobile phase in the ratio of 100% at a flow rate of 1.0 ml/min at a wavelength of 255nm. The developed method was validated according to ICH guidelines. Results:  The linearity was observed in the range of 20-100 µg/ml with a regression (R2) value of 0.999. Developed method was specific with no interactions and accurate with 100.11% for allopurinol and 99.54% for its related substance. The limit of detection for allopurinol was 2 µg/ml and for related substance was 0.0.1 µg/ml. The limit of quantification for allopurinol was 6 µg/ml and for related substance was 0.03 µg/ml respectively. The percentage relative standard deviation was found to be NMT 2 which indicates that the proposed method was precise and robust. Conclusion:  The developed method was simple, precise and accurate and can be successfully employed for the estimation of allopurinol in bulk and tablet dosage form.

Simultaneous Determination of Cholecalciferol and 25- Hydroxycholecalceferol in Lipid-based Self-nanoemulsifying formulations and Marketed Product Vi-de 3® by UHPLC-UV

2019 ◽  
Vol 16 (1) ◽  
pp. 100-109
Author(s):  
Ibrahim Aljuffali ◽  
Fahad Almarri ◽  
A. F. M. Motiur Rahman ◽  
Fars Kaed Alanazi ◽  
Musaed Alkholief ◽  
...  
Keyword(s):  
High Performance ◽  
Limit Of Detection ◽  
Simultaneous Estimation ◽  
Limit Of Quantification ◽  
Column Temperature ◽  
Related Substances ◽  
Accuracy And Precision ◽  
Regulatory Guidelines ◽  
25 Hydroxycholecalciferol

Background: The purpose of the current study was to develop a selective, precise, fast economical and advanced reverse phase ultra-high-performance liquid chromatography (UHPLC UV) method and validate it for the simultaneous estimation of cholecalciferol and its analogue 25- hydroxycholecalciferol in lipid-based self-nano emulsifying formulation (SNEDDS). Methods: The chromatographic separation was simply performed on a Dionex® UHPLC systems (Ultimate 3000, Thermo scientific) by using HSS C18 (2.1x50 mm, 1.8 µm) analytical column. The elution was carried out isocratically with the mobile phase consisting of acetonitrile and methanol in the ratio of 50:50 %v/v with a flow rate of 0.4 ml/min, followed by the UV detection at 265 nm. The injection volume was 1µl and the column temperature was maintained at 45°C. FDA regulatory guidelines were used to develop and validate the method. Results: The current developed UHPLC-UV method was found to be rapid (run time 2 min), and selective with the high resolution of cholecalciferol and 25-hydroxycholecalciferol (RT=0.530 min & 1.360 min) from different lipid matrices. The method was highly sensitive (Limit of Detection and Lower Limit of Quantification were 0.13 ppm & 0.51ppm, and 0.15 ppm & 0.54 ppm, respectively). The linearity, accuracy and precision were determined as suitable over the concentration range of 0.5-50.0 ppm for both the analytes. Conclusion: The proposed UHPLC-UV method can be used for the determination of cholecalciferol and 25-hydroxycholecalciferol in SNEDDS and marketed Vi-De 3® as pure forms (intact) with no interference of excipients or drug-related substances.

scholarly journals Evaluation of Pharmaceutical Quality of Mesalamine Delayed Release Tablets Using a New High Sensitivity Reversed-Phase UPLC Method for its Genotoxic/Aniline Impurity

2011 ◽  
Vol 8 (1) ◽  
pp. 167-179 ◽  
Author(s):  
Rakshit Kanubhai Trivedi ◽  
Mukesh C. Patel
Keyword(s):  
Detection Limit ◽  
Drug Product ◽  
Reversed Phase ◽  
Forced Degradation ◽  
Limit Of Quantification ◽  
Release Formulation ◽  
Pharmaceutical Quality ◽  
Delayed Release ◽  
Run Time

A reversed phase ultra performance liquid chromatography (UPLC) method was developed and validated for the quantification of aniline in mesalamine delayed-release tablets. The optimization of the experimental condition was carried out considering some important requirements like, detection limit, short run time and reproducibility. In the present study, isocratic reversed-phase UPLC method was developed for determination and separation of aniline from the drug product. The drug and impurity are well separated by using a reversed phase (Reprosil Gold C18-XBD) column and mobile phase comprising of buffer pH 6.0 and acetonitrile in the ratio of 90:10 v/v. Other UPLC parameters which were optimised are flow rate, 0.5 mL/min; detection wavelength, 200 nm; column oven temperature, 50°C and injection volume 7 µL. Stability indicating capability was also established by forced degradation experiments. The method was validated as per ICH guideline. LOQ (limit of quantification) concentration (18 ng/mL) was found precise with RSD of less than 2%. In essence, the present study provides an improved low detection limit and lower run time for evaluation of pharmaceutical quality of mesalamine delayed-release formulation. Moreover, the developed method was also successfully applied for quantification of aniline in mesalamine delayed-release formulation. The same method can also be used for determination of aniline from drug substances.

scholarly journals Ultra performance liquid chromatographic method for simultaneous quantitation of degradation products of telmisartan and hydrochlorothiazide in combination dosage form

2020 ◽  
Vol 11 (2) ◽  
pp. 2070-2082
Author(s):  
Narasimha Reddy G P ◽  
Sreenivasulu Reddy T ◽  
Sidda Reddy K ◽  
Shashi Kumar K N
Keyword(s):  
Mobile Phase ◽  
Method Development ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Drug Product ◽  
Wave Length ◽  
Stability Study ◽  
Limit Of Quantification ◽  
Pharmaceutical Dosage Forms ◽  
Stability Indicating

This work is intended to thrive a stability indicating Ultra performance liquid method for the estimation of (TLM) and (HCTZ) and degradation products pharmaceutical dosage forms. Separation was carried out on Zorbax Eclipse XDB C-18(50 x 2.1 mm, 1.7 ) column using a gradient method. Mobile phase A is 10mM KH2PO4 having 1% (v/v) of and mobile phase B is used in this work. 0.5 / minute is the flow of rate and at 271nm noticed wave length is monitored. Method development trails were carried out on six different columns. For specificity, limit of quantification, limit of detection, linearity, accuracy, method precision, robustness and stability this method is validated. Correlation coefficient of the impurities is more than 0.99. Stability indicating method confirmed that there were no interference of all impurities of TLM and HCTZ. Hence, developed LC method was stability indicating and well applied for drug product stability study as well as to quality monitoring.

scholarly journals Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants

2016 ◽  
Vol Volume 10 ◽  
pp. 2137-2154 ◽  
Author(s):  
Fidele Ntie-Kang ◽  
Conrad Veranso Simoben ◽  
Berin Karaman ◽  
Valery Fuh Ngwa ◽  
Philip Neville Judson ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Anticancer Agents ◽  
In Silico ◽  
Pharmacophore Modeling ◽  
Toxicity Assessment ◽  
In Silico Toxicity

scholarly journals Determination of Mesalamine Related Impurities from Drug Product by Reversed Phase Validated UPLC Method

2011 ◽  
Vol 8 (1) ◽  
pp. 131-148 ◽  
Author(s):  
Trivedi Rakshit Kanubhai ◽  
Patel Mukesh C ◽  
Kharkar Amit R
Keyword(s):  
Degradation Products ◽  
Drug Product ◽  
Gradient Elution ◽  
Reversed Phase ◽  
Forced Degradation ◽  
Limit Of Quantification ◽  
Release Formulation ◽  
Delayed Release ◽  
Related Substances

In the present study gradient reversed-phase UPLC method was developed for simultaneous determination and separation of impurities and degradation products from drug product. The chromatographic separation was performed on acquity UPLC BEH C18 column (50 mm×2.1 mm, 1.7 µm) using gradient elution. Other UPLC parameters which were optimised are flow rate, 0.7 mL/min; detection wavelength, 220 nm; column oven temperature, 40°C and injection volume 7 µL. Stability indicating capability was established by forced degradation experiments and separation of known degradation products. The method was validated as per International Conference on Harmonization (ICH) guideline. For all impurities and mesalamine, LOQ (limit of quantification) value was found precise with RSD (related standard daviation) of less than 2.0%. In essence, the present study provides an improved low detection limit and lower run time for evaluation of pharmaceutical quality of mesalamine delayed-release formulation. Moreover, the developed method was successfully applied for quantification of impurities and degradation products in mesalamine delayed-release formulation. The same method can also be used for determination of related substances from mesalamine drug substance.

Sign in / Sign up

Export Citation Format

Share Document