Identification of impurities in ivermectin bulk material by mass spectrometry and NMR

Beasley, Christopher A.; Hwang, Tsang‐Lin; Fliszar, Kyle A.; Abend, Andreas; McCollum, David G.; Reed, Robert A.

doi:10.1016/j.jpba.2006.02.021

Cited by 11 publications

(7 citation statements)

References 21 publications

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“…NMR measurements were performed on a Bruker Avance III HDX 500 MHz spectrometer ('Bruker-500') equipped Distance between the corresponding peaks in the IP + AP subspectrum and the IP − AP subspectrum. d In the parentheses, the first character corresponds to the ring (A, B, C), the second to the position (1,2,3), and the third to the signal set (M, major; m, minor), see Figure 9.…”

Section: Generalmentioning

confidence: 99%

“…in conjunction with other orthogonal techniques. Such tasks involve a wide technical scope, including the quantification of the components in a formulation, [1] the identification of impurities, [2][3][4][5] stability studies, [6,7] the compatibility study of a drug substance with an excipient, [8] and the identification of metabolites. [9,10] NMR spectroscopy plays a significant role in drug discovery projects, for example, in fragment-based drug discovery [11] or in the identification of pharmacophores.…”

Section: Introductionmentioning

confidence: 99%

“…Even though the main role of NMR, generally speaking, is to support medicinal chemistry projects via the structure elucidation of small molecules using liquid‐state NMR spectroscopy, NMR has been used for a long time to tackle many other pharmaceutical R&D&QC‐related analytical issues, often in conjunction with other orthogonal techniques. Such tasks involve a wide technical scope, including the quantification of the components in a formulation, [ 1 ] the identification of impurities, [ 2–5 ] stability studies, [ 6,7 ] the compatibility study of a drug substance with an excipient, [ 8 ] and the identification of metabolites. [ 9,10 ] NMR spectroscopy plays a significant role in drug discovery projects, for example, in fragment‐based drug discovery [ 11 ] or in the identification of pharmacophores.…”

Section: Introductionmentioning

confidence: 99%

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On the utility of nonuniformly sampled two‐dimensional NMR spectra in the pharmaceutical industry

Szigetvári

Szántay

2020

Magnetic Reson in Chemistry

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In this work, we discuss representative examples of the application of nonuniform sampling (NUS) in small-molecule structure determination in a pharmaceutical research and development and quality control setting. We demonstrate the advantages of NUS over traditional sampling in various industrial applications of nuclear magnetic resonance (NMR). We propose an optimal trade-off between the quality and the time efficiency of 'routine' measurements, as demonstrated via a test sample of vinpocetine analyzed on a 'work horse' NMR spectrometer. In addition, we present case studies where the application of NUS contributed significantly to the successful completion of some challenging structure determination task at hand. To that end, in some cases, we combined NUS with a method of decoupling in the indirect dimension that gives 'constant time' nuclear Overhauser effect spectroscopy (NOESY) and 'constant time' heteronuclear multiple bond correlation (HMBC) spectra. NUS proved to be superior over traditional sampling even for the analysis of trace impurities, where the need to cope with a thousand-fold or even larger dynamic range and low signal-to-noise ratio for the impurity signals is quite a challenge.

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Section: Generalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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On the utility of nonuniformly sampled two‐dimensional NMR spectra in the pharmaceutical industry

Szigetvári

Szántay

2020

Magnetic Reson in Chemistry

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“…Bhanu Raman et al [48] detected a major process-related impurity associated with the synthesis of ezetimibe by LC-MS. They proposed Avermectins 24-demethylH2B1a, 3'-demethylH2B1a, 3"-demethyl H2B1a and 24a-hydroxy B2a [50] the structure of impurity to be 2-(4-hydroxybenzyl)-N, 5-bis-(4-fluorophenyl)-5-hydroxypentanamide based on LC-MS/MS studies and accurate mass data. The proposed structure was confirmed with the help of the NMR and IR analyses of a synthetically obtained sample.…”

Section: Hplc Tandem Mass Spectrometry (Lc-ms/ms)mentioning

confidence: 99%

“…Cefadroxil was used as a model compound for the evaluation of a predictive strategy for the production and elucidation of impurities and degradants induced by acid, base, and heat. Andreas Abend et al [50] identified and characterized four process impurities in bulk of Avermectin, using a combination of LC-MS and LC-MS/MS. The result indicates that these impurities are a product of biosynthesis of avermectin.…”

Section: Hplc Tandem Mass Spectrometry (Lc-ms/ms)mentioning

confidence: 99%

Recent Advances in Characterization of Impurities - Use of Hyphenated LC-MS Technique

Vyas¹,

Ghate²,

Ukawala

2010

CPA

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Profiling of impurities in pharmaceutical products is an important part of the pharmaceutical manufacturing process and it is a regulatory expectation. Impurities may influence the safety and efficacy of the pharmaceutical products. Estimation of the impurity of pharmaceuticals provides excellent means for drug authorities to control the manufacturing process. To meet the challenges and to build high degree of purity in drug substances and drug products, it is required to carry out all the investigations for standards of drugs and impurities to get significant results. Different methods are available for impurity profiling; the most common analytical methods are based upon spectroscopic and chromatography separation techniques. One of the powerful tools of impurity profile is liquid chromatography (LC) coupled with mass spectroscopy (MS), and it is employed for the identification of impurities, natural products, drug metabolites, and proteins. LC-MS offers selectivity and specificity in both the chromatographic separation and detection steps, and is found as necessary steps to measure compounds at extremely low concentrations. LC-MS is steadily applied to scrutinize impurity during pharmaceutical product development and manufacturing process to support the safety evaluation of batches used in clinical studies. In this review, strategies for impurity profiling of pharmaceuticals with the applications of LC-MS, LC-MS/MS, LC-ESI/MS and LC-TOF/MS methods will be critically reviewed and discussed.

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Fragmentation of Drugs and Pesticides

2017

Interpretation of MS‐MS Mass Spectra of Drugs and Pesticides

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Identification of impurities in ivermectin bulk material by mass spectrometry and NMR

Cited by 11 publications

References 21 publications

On the utility of nonuniformly sampled two‐dimensional NMR spectra in the pharmaceutical industry

On the utility of nonuniformly sampled two‐dimensional NMR spectra in the pharmaceutical industry

Recent Advances in Characterization of Impurities - Use of Hyphenated LC-MS Technique

Fragmentation of Drugs and Pesticides

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