scholarly journals Identification of Tartaric Acid Adduct Impurities in Dipyridamole Capsule Formulation Related Substances Method

2021 ◽  
Vol 33 (2) ◽  
pp. 307-313
Author(s):  
J. NAGADEEP ◽  
P. KAMARAJ ◽  
M. ARTHANAREESWARI ◽  
P.A. VIVEKANAND
Keyword(s):  
Tartaric Acid ◽  
Degradation Products ◽  
Simple Procedure ◽  
Control Release ◽  
Capsule Formulation ◽  
Related Substance ◽  
Relative Retention ◽  
Related Substances ◽  
Shelf Life Stability ◽  
Acid Adduct

Two tartaric acid adduct degradation products namely dipyridamole tartaric acid monoester and dipyridamole ditartaric acid ester are observed in a dipyridamole capsule formulation. The adduct impurities are inevitable in the formulation due to the interaction of multilayers of dipyridamole on tartaric acid pellets. Present study reported a simple procedure for generating these two major adducts degradation products from a mixture of dipyridamole drug substance and tartaric acid by stress study. The obtained stress mixture was characterized by liquid chromatography-tandem mass spectrometry (LC-MS) to assure the identity of adduct degradant impurities. The obtained solid stress mixture was stable for more than one year and the prepared solution can be used as reference solution to identify both the degradants during related substance analysis. Practically, the identification of tartaric acid degradants applied to the British pharmacopeia monograph related substances method, where no mechanism for identification of these adduct impurities was described. This study establishes relative retention times for the British pharmacopeia method, which enables the chemist to monitor these two major degradants during quality control release testing and shelf life stability. The same kind of experimental approach for identifying tartaric acid adduct impurities in the British pharmacopeia method can be extended to any of the in-house laboratory-developed related substance methods.

Synthesis and Characterization of Potential and Degraded Impurities of Regadenoson

2020 ◽  
Vol 16 (8) ◽  
pp. 1130-1139
Author(s):  
Singaram Sathiyanarayanan ◽  
Chidambaram Subramanian Venkatesan ◽  
Senthamaraikannan Kabilan
Keyword(s):  
Mass Spectra ◽  
Degradation Products ◽  
Hplc Method ◽  
Forced Degradation ◽  
Spectroscopic Techniques ◽  
A2a Adenosine Receptor ◽  
Degradation Study ◽  
Related Substances ◽  
Adenosine Receptor Agonist

Background: Regadenoson is an A2A adenosine receptor agonist that is a coronary vasodilator and commonly used as a pharmacologic cardiac stressing agents. Methods: HPLC method was used for the analysis of related substances. The degraded impurities during the process were isolated and characterized by IR, Mass and NMR spectral analysis. Results: Forced degradation study of regadenoson under conditions of hydrolysis (neutral, acidic and alkaline) and oxidations suggested in the ICH Q1A(R2) was accomplished. The drug showed significant degradation under all the above conditions. On the whole, five novel degradation products were found under diverse conditions along with process related impurities which were not reported earlier. Conclusion: All the degradation products were well characterized by using advanced spectroscopic techniques like IR, 1H NMR, 13C NMR and Mass spectra. The identification of these impurities will be productive for the quality control during the production and stability behavior of the regadenoson drug substance.

Identification, Characterization, and Quantification of Impurities of Safinamide Mesilate: Process-Related Impurities and Degradation Products

2017 ◽  
Vol 100 (4) ◽  
pp. 1029-1037 ◽  
Author(s):  
Liang Zou ◽  
Lili Sun ◽  
Hui Zhang ◽  
Wenkai Hui ◽  
Qiaogen Zou ◽  
...  
Keyword(s):  
Degradation Products ◽  
Hplc Method ◽  
Formation Mechanisms ◽  
Stability Indicating ◽  
Related Impurities ◽  
Related Substances ◽  
Water Ph ◽  
Bulk Drug ◽  
First Time

Abstract The characterization of process-related impurities and degradation products of safinamide mesilate (SAFM) in bulk drug and a stability-indicating HPLC method for the separation and quantification of all the impurities were investigated. Four process-related impurities (Imp-B, Imp-C, Imp-D, and Imp-E) were found in the SAFM bulk drug. Five degradation products (Imp-A, Imp-C, Imp-D, Imp-E, and Imp-F) were observed in SAFM under oxidative conditions. Imp-C, Imp-D, and Imp-E were also degradation products and process-related impurities. Remarkably, one new compound, identified as (S)-2-[4-(3-fluoro-benzyloxy) benzamido] propanamide (i.e., Imp-D), is being reported here as an impurity for the first time. Furthermore, the structures of the aforementioned impurities were characterized and confirmed via IR, NMR, and MS techniques, and the most probable formation mechanisms of all impurities proposed according to the synthesis route. Optimum separation was achieved on an Inertsil ODS-3 column (250 × 4.6 mm, 5 μm), using 0.1% formic acid in water (pH adjusted to 5.0) and acetonitrile as the mobile phase in gradient mode. The proposed method was found to be stability-indicating, precise, linear, accurate, sensitive, and robust for the quantitation of SAFM and its process-related substances, including its degradation products.

scholarly journals Enzyme Immunoassay for Aflatoxin B1-Lysine Adduct and Its Validation

2001 ◽  
Vol 84 (5) ◽  
pp. 1465-1474 ◽  
Author(s):  
Nayak Sujatha ◽  
Sarilla Suryakala ◽  
Beedu Sashidhar Rao
Keyword(s):  
Enzyme Immunoassay ◽  
Aflatoxin B1 ◽  
Retention Time ◽  
Simple Procedure ◽  
Molar Ratio ◽  
Rat Serum ◽  
In Vitro Synthesis ◽  
Coating Antigen ◽  
Relative Retention

Abstract A simple procedure was developed for in vitro synthesis and characterization of aflatoxin B1-lysine adduct using aflatoxin B1, N-α-acetyl lysine and m-chloroperbenzoic acid (MCPBA). At a molar ratio of 1:16 (aflatoxin B1:N-α-cetyl lysine), the recovery of adduct was 62%. Analysis of the adduct by thinlayer chromatography showed a single spot (Rf= 0). Absorption spectra of the adduct showed 2 peaks at 275 and 335 nm. Liquid chromatographic (LC) analysis of th AFB1-lysine adduct showed a relative retention time of 2.1 min. Using the same epoxidation procedure, BSA-AFB1 adduct and ovalbumin-AFB1 adduct were synthesized for production of antibodies and as coating antigen, respectively. Control rat serum, spiked with AFB1-lysine adduct and subjected to LC analysis showed a retention time of 2.1 min, which is similar to that of AFB1-lysine reference standard, synthesized. Further, enzymatically hydrolyzed, control rat serum spiked with BSA-AFB1 adduct showed 2 peaks with retention times of 2.1 and 2.7 min. Based on the LC analysis, recovery of BSA-AFB1 in terms of AFB1-lysine adducts was 67 ± 5%. The major peak (2.1 min) accounted for 72% of the adduct; the second minor peak (2.7 min) accounted for 28% of the total AFB1-lysine adducts formed. Stability studies on the AFB1-lysine adduct synthesized, indicated that it was stable for 1 month. Antibody capture assay showed an absorbance of 0.9 to 1.0 at a dilution of 1:50 000 when ovalbumin-AFB1 was used as a coating antigen. Indirect competitive ELISA showed 50% displacement (IC50) of the antibodies at a concentration of 13 ng AFB1-lysine, whereas the IC50 for AFB1 was 7 ng. The recovery of AFB1-lysine adduct spiked to control rat serum followed by enzymatic hydrolysis and immunoanalysis (indirect ELISA) was 93 ± 6%. The enzyme immunoassay was validated by a rodent model, in which the animals were exposed to aflatoxin B1 (20 μg AFB1/kg body mass/day). The level of AFB1-lysine adduct in the rat serum was 27.3 ± 4.37 μg/mg albumin.

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.

scholarly journals Fast and selective HPLC-DAD method for determination of pholcodine and related substances

2011 ◽  
Vol 30 (2) ◽  
pp. 139 ◽  
Author(s):  
Ana Petkovska ◽  
Hristina Babunovska ◽  
Marina Stefova
Keyword(s):  
Quality Control ◽  
Degradation Products ◽  
Ammonium Hydroxide ◽  
Gradient Elution ◽  
Reversed Phase ◽  
Real Sample Analysis ◽  
Related Substances ◽  
Structural Analogues ◽  
Reliable Methods

Quality control of pharmaceuticals requires development of fast, efficient and reliable methods for determination of active compounds as well as known and very often unknown impurities within defined concentration ranges. In this work, a simple and rapid HPLC-UV-DAD method for identification and quantification of pholcodine process related impurities and some degradation products was developed and validated. Pholcodine and its five structural analogues such as morphine, codeine, thebaine, oripavine, and papaverine were separated in less than 10 minutes using reversed phase LiChrospher C-8 column. For optimal chromatographic performance with reproducible retention times, gradient elution with 2% ammonium hydroxide in water and acetonitrile was used. The method was validated by establishing its selectivity, specifity, sensitivity, linearity, intra- and inter-day precision and robustness. All tested parameters confirmed that the method is suitable for determination of pholcodine and its five impurities in pharmaceutical drug samples. The results obtained from real sample analysis give support to the suitability of the proposed method for the purpose of quality control.

New Rapid Stability indicating RP-UPLC Method for the Determination of Olaparib, its Related Substances and Degradation Products in Bulk drug and Dosage Form

2019 ◽  
Vol 14 ◽  
pp. 492-503
Author(s):  
DasameswaraRao Kavitapu ◽  
Arthanareeswari Maruthapillai ◽  
S. Devikala ◽  
J. Arockia Selvi ◽  
M. Tamilselvi ◽  
...  
Keyword(s):  
Dosage Form ◽  
Degradation Products ◽  
Stability Indicating ◽  
Related Substances ◽  
Bulk Drug

Preparation and Characterization of Four Major Novel Degradation Products of Pralatrexate Injection and Validation of HPLC-UV Method

2019 ◽  
Vol 15 (7) ◽  
pp. 724-737
Author(s):  
Regella Venkata Rama Prabhakara Sastry ◽  
Chidambaram Subramanian Venkatesan ◽  
Bhetanabhotla Sarveswara Sastry ◽  
Singaram Sathiyanarayanan ◽  
Sanapati Murali
Keyword(s):  
Degradation Products ◽  
Drug Product ◽  
Light Stress ◽  
Hplc Method ◽  
Dihydrogen Phosphate ◽  
Liquid Formulation ◽  
Stability Indicating ◽  
Related Substances ◽  
Validation Parameters

Background: Four major degradation products (1-4) of pralatrexate injection were formed under hydrolytic and light stress conditions. The impurities 1 and 2 were the potential photo degradation products and the impurities 3 and 4 were the potential hydrolytic degradation products. Objective: To prepare and characterize the novel degradation impurities 1, 2, 3 and 4 of pralatrexate injection using NMR, HR MS and IR techniques; and to develop and validate stability indicating analytical reverse phase HPLC-UV method for quantitative simultaneous determination of potential degradation impurities, related substances of pralatrexate and pralatrexate active in pralatrexate liquid formulation. Methods: Gradient HPLC-UV method was developed for the quantification of degradation impurities, related substances and pralatrexate in pralatrexate injection. The separation was achieved on C18 column (250 mm X 4.6 mm, 5µm) using a mobile phase composed of sodium dihydrogen phosphate monohydrate in water (pH 3.0; 0.01M) and methanol. The components were monitored by the UVvisible detector at 242 nm with a flow rate of 1.0 mL/min. Results: The method validation parameters such as accuracy, selectivity, linearity, LOD, LOQ, precision, ruggedness and robustness were demonstrated successfully for pralatrexate and its degradation impurities. The stability-indicating capability of the developed HPLC method was demonstrated by adequate separation of all potential pralatrexate related substances from pralatrexate stressed drug product samples. Conclusion: The developed stability indicating HPLC method was found to be suitable for the simultaneous quantitative determination of potential degradation impurities and related substances of pralatrexate and pralatrexate active in pralatrexate liquid formulation.

Analytical Quality by Design (AQbD) Approach Based HPTLC Method for Quantification of Fisetin with Superior Recovery in Formulations

2020 ◽  
Vol 16 (2) ◽  
pp. 149-157
Author(s):  
Thasleem Moolakkadath ◽  
Mohd Aqil ◽  
Syed Sarim Imam ◽  
Abdul Ahad ◽  
Arshiya Praveen ◽  
...  
Keyword(s):  
High Performance ◽  
Degradation Products ◽  
Active Pharmaceutical Ingredient ◽  
Stress Conditions ◽  
Alkaline Stress ◽  
Capsule Formulation ◽  
Ich Guidelines ◽  
Phase Combination ◽  
Layer Chromatography ◽  
Hptlc Method

Background: A stability indicating high-performance thin layer chromatography (HPTLC) method was developed for the evaluation of fisetin (FIS) in active pharmaceutical ingredient (API) and marketed capsule formulation in accordance with the ICH guidelines. Methods: The mobile phase combination toluene: ethyl acetate: formic acid: methanol (3: 5.5: 1: 0.5 v/v/v/v) was optimized with the aid of AQbD approach. The absorbance mode at 254 nm was chosen for densitometric analysis as it gives a compact spot of FIS at Rf value of 0.74. Results: The R2 value obtained from the linear regression equation of calibration plots made by taking the spot in the concentration range of 100-1400 ng/spot was found to be 0.9993. The observed LOD and LOQ value was found to be 29.8 ng/spot and 98.5 ng/spot, respectively. The exposure of FIS to various stress conditions revealed the fact that the drug is stable in photochemical and dry heat stress conditions without any degradation. The drug-exposed to acidic, alkaline and oxidative stress was found to be degraded into different degradation products with the highest degradation was found in alkaline stress. All degradation products were observed to be fairly separated from well-resolved parent peak of FIS. Conclusion: The developed HPTLC method have shown well-resolved peaks and also shown good recovery in the compound FIS as well as FIS formulation.

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