Analytical challenges and recent advances in the identification and quantitation of extractables and leachables in pharmaceutical and medical products

Singh, Gagandeep; Lu, Dujuan; Liu, Chongming; Hower, Danny

doi:10.1016/j.trac.2021.116286

Cited by 22 publications

(14 citation statements)

References 116 publications

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“…Volatile metabolites include lipids, furan and pyrrole derivatives, alcohols, ketones, aldehydes, esters, various heterocyclic compounds, isocyanates, isothiocyanates, sulfides, and hydrocarbons with 1 to 12 carbons (Villas‐Bôas et al., 2005). Numerous semi‐ and nonvolatile metabolites, such as sugars, sugar phosphates, sugar alcohols, flavonoids, organic acids, lipids, amino acids, peptides, long‐chain alcohols, alkaloids, amines, and amides, can also be investigated using efficient derivatization techniques involving alkylation, acylation, or silylation reactions (Singh et al., 2021; Villas‐Bôas et al., 2005).…”

Section: Resultsmentioning

confidence: 99%

Phytoconstituents from Moringa oleifera fruits target ACE2 and open spike glycoprotein to combat SARS‐CoV‐2: An integrative phytochemical and computational approach

Siddiqui

Ahmad

Alaidarous

et al. 2022

Journal of Food Biochemistry

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Therapeutic drugs based on natural products for the treatment of SARS-CoV-2 are currently unavailable. This study was conducted to develop an anti-SARS-CoV-2 herbal medicine to face the urgent need for COVID-19 treatment. The bioactive components from ethanolic extract of Moringa oleifera fruits (MOFs) were determined by gas chromatography-mass spectroscopy (GC-MS). Molecular-docking analyses elucidated the binding effects of identified phytocomponents against SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) and human ACE2 receptor (PDB ID: 1R42) through the Glide module of Maestro software. GC-MS analysis unveiled the presence of 33 phytocomponents. Eighteen phytocomponents exhibited good binding affinity toward ACE2 receptor, and thirteen phytocomponents had a high affinity with spike glycoprotein. This finding suggests that the top 11 hits (Docking score ≥ −3.0 kcal/ mol) could inhibit SARS-CoV-2 propagation. Intriguingly, most of the phytoconstituents displayed drug-likeness with no predicted toxicity. However, further studies are needed to validate their effects and mechanisms of action. Practical applicationsMoringa oleifera (MO) also called "drumstick tree" has been used as an alternative food source to combat malnutrition and may act as an immune booster. GC-MS analysis unveiled that ethanolic extract of Moringa oleifera fruits (MOFs) possessed 33 active components of pyridine, aromatic fatty acid, oleic acid, tocopherol, methyl ester, diterpene alcohol, triterpene and fatty acid ester and their derivatives, which have various pharmacological and medicinal values. Virtual screening study of phytocomponents of MOF with human ACE2 receptor and SARS-CoV-2 spike glycoprotein exhibited good binding affinity. Based on molecular docking, the top 11 hits (Docking score ≥-3.0 kcal/mol) might serve as potential lead molecules in antiviral drug development.Intriguingly, most of the phytoconstituents displayed drug-likeness with no predicted toxicity. Thus, MOF might be used as a valuable source for antiviral drug development to combat COVID-19, an ongoing pandemic.

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Section: Resultsmentioning

confidence: 99%

Phytoconstituents from Moringa oleifera fruits target ACE2 and open spike glycoprotein to combat SARS‐CoV‐2: An integrative phytochemical and computational approach

Siddiqui

Ahmad

Alaidarous

et al. 2022

Journal of Food Biochemistry

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“…The m/z list of the background ions was used as the exclusion list in the data-dependent MS/MS acquisition method for the extraction sample analysis, while those only extraction sample related mass lists were used as targeted inclusion list in the subsequent data-dependent MS/MS acquisition. The 40% ethanol extraction samples were reinjected 4 times for repeated sample interrogation using the data-dependent MS/MS acquisition method with the updated exclusion and inclusion list and 4 different HCD collision energies (7,15,30,50). This data acquisition strategy allows us to generate the greatest number of highquality MS/MS fragment ion spectra for the precursor ions only related to the extraction samples and eliminate MS/MS spectra from the background ions present in both 40% ethanol control sample and the extraction samples.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

A Chemical Characterization Workflow for Nontargeted Analysis of Complex Extracts from Polymer Based Medical Device Using High Resolution LC/MS

Kiley

Kullar

et al. 2023

ACS Biomater. Sci. Eng.

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The chemical characterization of extractables and leachables (E&Ls) is an important aspect of biosafety and biocompatibility assessment in medical device industry. The advent of the body-contact use of medical devices in patient treatment has introduced a potential source for extractables and leachables as these medical devices are comprised of various polymeric materials. Several industry working groups, the FDA and USP, have recognized the guidance for chemical characterizations and nontargeted analysis of medical device extracts, such as ISO 10993–18:2020. The MS application of nontargeted analysis has played a critical role in understanding the E&Ls from medical device extracts. However, there have been very few reports about the MS based workflow with nontargeted analysis for medical device extracts and there is little guidance about the exact methodologies which should be used, even though there is an urgent need for a clearly defined process for the identification of medical device extracts. In this study, we demonstrated an analytical LC/MS (liquid chromatography/mass spectrometry) workflow using high resolution Exploris120 Orbitrap instrument for data acquisition and Compound Discoverer 3.3 intelligent software for data processing to profile the polymer related E&Ls from a balloon dilation catheter device extracted with 40% ethanol. An E&L ID workflow combining LC separation, data-informed MS acquisition strategy, MS information mining (including adduct ions, MS information from both electrospray ionization (ESI) (+) and ESI (−), in-source fragmentation, common fragment ions (CFIs), common neutral losses (CNLs), and in silico MS simulation was described with intelligent software processing and manual data interpretation. The workflow developed in this study was proven to be effective to provide a comprehensive profile of polymer related degradation products, polymer impurities and additives including surfactants, UV curing agent, antioxidants, and plasticizers for the device analyzed. The classification of E&L compounds using CFIs and CNLs was very effective to facilitate the identification of polymer related impurities and extract the polymer related impurities with common structures in a large data result set.

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“…Numerous literature and discussions exist addressing challenges in compound identification and how to improve quantification practices which reflects the importance of these aspects. 17 , 18 This strong focus on the “analytical part” leads to some bias in the perception about other present difficulties in E&L testing. For example, most of the materials used in the biopharmaceutical industry have been used for decades and most of “their” extractables are already known and can be readily identified or even predicted using available databases.…”

Section: Methodsmentioning

confidence: 99%

X‐ray sterilization of biopharmaceutical manufacturing equipment—Extractables profile of a film material and copolyester Tritan™ compared to gamma irradiation

Menzel

Dorey²,

Maier

et al. 2021

Biotechnology Progress

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The biopharmaceutical industry gains enormous flexibility in production processes by using sterilized preassembled single-use devices. Gamma irradiation is an established sterilization technology that may be restricted in the future by the availability of 60 Co as irradiation source and irradiation capacities. X-ray technology is considered an alternative type of radiation for sterilizing SU equipment. In the context of extractables and leachables-one concern connected with the use of single-use process equipment-the effect of X-ray irradiation on the extractables profile of the materials needs to be compared to established gamma irradiation to qualify this alternative technology. An approach is presented to obtain robust and comprehensive extractables data for materials used in SU devices after sterilization either using X-ray or gamma irradiation. A careful selection of the test items and the test design allows a one-to-one comparison of data obtained from a combination of orthogonal analytical techniques. The extractables of a modern SU film material and the copolyester Tri-tan™ are evaluated. The data presented allow a risk evaluation on the safety of this new sterilization modality for biopharmaceutical applications. It is demonstrated that the extractables profile of a polymer is not affected by the type of irradiation used for sterilization.

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Analytical challenges and recent advances in the identification and quantitation of extractables and leachables in pharmaceutical and medical products

Cited by 22 publications

References 116 publications

Phytoconstituents from Moringa oleifera fruits target ACE2 and open spike glycoprotein to combat SARS‐CoV‐2: An integrative phytochemical and computational approach

Phytoconstituents from Moringa oleifera fruits target ACE2 and open spike glycoprotein to combat SARS‐CoV‐2: An integrative phytochemical and computational approach

A Chemical Characterization Workflow for Nontargeted Analysis of Complex Extracts from Polymer Based Medical Device Using High Resolution LC/MS

X‐ray sterilization of biopharmaceutical manufacturing equipment—Extractables profile of a film material and copolyester Tritan™ compared to gamma irradiation

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