Determination of Impurities in Perampanel Bulk Drugs by High-Performance Liquid Chromatography and Gas Chromatography

2020 ◽  
Vol 16 ◽  
Author(s):  
Yun-Yan Xia ◽  
Qiao-Gen Zou ◽  
Yu-Fei Yang ◽  
Qian Sun ◽  
Cheng-Qun Han
Keyword(s):  
Gas Chromatography ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Quantitative Detection ◽  
Dihydrogen Phosphate ◽  
Phosphate Solution ◽  
Related Impurities ◽  
Bulk Drug

Background: High-performance liquid chromatography (HPLC) method has been used to detect related impurities of perampanel. However, the detection of impurities is incomplete, and the limits of quantification and detection are high. A sensitive, reliable method is in badly to be developed and applied for impurity detection of perampanel bulk drug. Objective: Methodologies utilising HPLC and gas chromatography (GC) were established and validated for quantitative determination of perampanel and its related impurities (a total of 10 impurities including 2 genotoxic impurities). Methods: The separation was achieved on a Dikma Diamonsil C18 column (250 mm × 4.6 mm, 5 μm) with the mobile phase of 0.01 mol/L potassium dihydrogen phosphate solution (A) and acetonitrile (B) in gradient elution mode. The compound 2-bromopropane was determined on an Agilent DB-624 column (0.32 mm × 30 m, 1.8 μm) by electron capture detector (μ-ECD) with split injection ratio of 1:5 and proper gradient temperature program. Result: Both HPLC and GC methods were established and validated to be sensitive, accurate and robust according to International Council for Harmonization (ICH) guidelines. The methods developed were linear in the selected concentration range (R 2≥0.9944). The average recovery of all impurities was between 92.6% and 103.3%. The possible production mechanism of impurities during the synthesis and degradation processes of perampanel bulk drug was also discussed. Five impurities were analyzed by liquid chromatography–mass spectrometry (LC-MS). Moreover, two of them were simultaneously characterized by LC-MS, IR and NMR. Conclusion: The HPLC and GC methods were developed and optimized, which could be applied for quantitative detection of the impurities, and further stability study of perampanel.

Identification, characterization, and determination of process-related impurities in Minodronic Acid bulk drug

2021 ◽  
Vol 17 ◽  
Author(s):  
Shi Anan ◽  
Zou Qiaogen ◽  
Gao Pan
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Limit Of Detection ◽  
Hplc Method ◽  
Quantitative Detection ◽  
Resonance Spectroscopy ◽  
Related Impurities ◽  
Minodronic Acid

Background: Minodronic acid (MA) is a third-generation nitrogen-containing heterocyclic bisphosphonate used to treat osteoporosis. In the process of starting materials research and preparation, the key intermediate impurities and degradation impurities have a great impact on the quality control of the drug. Objective: A sensitive, reliable high-performance liquid chromatography (HPLC) method was developed and validated for the quantitative determination of MA and its related impurities (a total of 6 compounds, including 2 new impurities). Methods: The separation was achieved on an InertSustain ODS-4 C18 (250 mm×4.6 mm, 5 μm) column using the mixture of 0.01 mol/L sodium pyrophosphate and 1 mmol tetrabutylammonium phosphate (the mobile phase pH was adjusted to 7.80 by phosphonic acid). Results: The quantitative analytical method was fully validated with respect to linearity (r>0.999), sensitivity (limit of detection<35 ng/mL), precision, accuracy (the recovery was between 98.7% and 104.2%), and robustness. Six process-related impurities in Minodronic Acid (MA) bulk drugs were determined by high-performance liquid chromatography (HPLC). Furthermore, except for two starting materials, other four impurities were identified and characterized as 2-(imidazo[1,2-a] pyridin-3-yl) ethyl acetate (Imp-C), 2-(imidazo [1,2-a] pyridin- 3-yl)acetic acid (Imp-D), 3-(2-hydroxy-2,2- diphosphonoethyl)-4H-imidazo [1,2-a] pyridine -4- oxide (Imp-E) and 2,5- Dihydroxy- 3,6-bis(imidazo[1,2-a] pyridine-3-yl methyl) -2,5-dioxo-1,4,2,5- dioxoDiphosphonium-3,6-diyl) bisphosphonic acid (Imp-F) using liquid chromatograph-mass spectrometer (LC-MS), MS/MS, Infrared Radiation and Nuclear Magnetic Resonance spectroscopy (1H-NMR and 13C-NMR). To the best of our knowledge, two of them (Imp-E and Imp-F) are new compounds and have not been reported previously. Conclusion: The HPLC method was developed and optimized, which could be applied for quantitative detection of the impurities, and further quality evaluation of MA.

scholarly journals Synthesis, Isolation and Characterization of Process-Related Impurities in Oseltamivir Phosphate

2012 ◽  
Vol 9 (1) ◽  
pp. 113-120 ◽  
Author(s):  
Yogesh Kumar Sharma ◽  
Dau Dayal Agarwal ◽  
Sudesh Bhure ◽  
Sanjay Singh Rathore ◽  
Chakravir Rawat ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Mass Number ◽  
Reverse Phase ◽  
Related Impurities ◽  
Isolation And Characterization ◽  
Bulk Drug ◽  
Oseltamivir Phosphate

Three known impurities in oseltamivir phosphate bulk drug at level 0.1% (ranging from 0.05-0.1%) were detected by gradient reverse phase high performance liquid chromatography. These impurities were preliminarily identified by the mass number of the impurities. Different experiments were conducted and finally the known impurities were synthesized and characterized.

Quantitative Determination of Vitamin E Isomers using Gas Chromatography, High Performance Liquid Chromatography and High Performance Thin Layer Chromatography

2017 ◽  
Vol 54 (3) ◽  
pp. 294
Author(s):  
Hari Ramakrishnan K. ◽  
Janaky Ranjithkumar
Keyword(s):  
Gas Chromatography ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Vitamin E ◽  
Thin Layer ◽  
Thin Layer Chromatography ◽  
High Performance ◽  
Highly Sensitive ◽  
Layer Chromatography

Vitamin E, the fat soluble vitamin is present naturally in some foods and added in food supplements, nutraceuticals etc due to its vital biological function as an antioxidant. Various methods are available for the analysis of vitamin E. Especially High Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC) are exclusively used for the quantitative evaluation of vitamin E, which has also identified the four different isomeric forms of this vitamin. The rate of losses of this vitamin during food processing and analysis, in addition to their transient dynamics, presents complexities in developing a highly sensitive procedure for their separations. Though effective, HPLC instrument is expensive and comparatively cumbersome. In this prospective, the study was to evaluate the usefulness of High Performance Thin Layer Chromatography (HPTLC) in the analysis of vitamin E. There are methods available using Thin Layer Chromatography for its analysis, but they are not sensitive enough to identify the isomeric forms of vitamin E. In this HPTLC method, the different isomeric forms of vitamin E - α, β, γ and δ were identified. This technique shall be considered as an alternative to the other methods such as HPLC and GC.

Simplified determination of serotonin in plasma by liquid chromatography with electrochemical detection.

1984 ◽  
Vol 30 (1) ◽  
pp. 131-135 ◽  
Author(s):  
P C Tagari ◽  
D J Boullin ◽  
C L Davies
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Human Plasma ◽  
Electrochemical Detection ◽  
High Performance ◽  
Carcinoid Syndrome ◽  
Quantitative Detection ◽  
Chromatographic Purification ◽  
Hydroxyindoleacetic Acid

Abstract This simplified determination of serotonin in human plasma involves "high-performance" liquid chromatography with electrochemical detection. Deproteinated samples of platelet-poor plasma are injected directly into the chromatograph without preliminary chromatographic purification. The limit of quantitative detection of serotonin in plasma is 5 nmol/L (equivalent to 250 fmol injected). Intra- and inter-assay CVs ranged from 5.6% to 7.7% and 3.5% to 14.9%, respectively, for concentrations of serotonin from 0.02 to 10.0 mumol/L. Results agreed well with those by spectrofluorometry, both for plasma standards (r = 0.985, range 100 nmol/L to 100 mumol/L) and for pathological samples obtained from four carcinoid syndrome patients (r = 0.964). The method is also applicable to the concurrent measurement of 5-hydroxytryptophan and 5-hydroxyindoleacetic acid.

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