ABSTRACT
BACKGROUND: Xylazine is an increasingly common adulterant in the North American unregulated drug supply that is associated with adverse health outcomes (e.g., skin infections, overdose). However, there are significant knowledge gaps regarding how xylazine was initially identified and how syringe services program (SSP) staff and clients (people who use drugs) responded to its emergence. METHODS: From June-July 2023, we conducted qualitative interviews with medical (e.g., clinicians) and frontline SSP staff (e.g., outreach workers) and adult clients with a history of injection drug use at a Miami-based SSP. Inductive memos identified emergent codes; thematic analysis involving team consensus established final themes. RESULTS: From interviews with SSP staff (n = 8) and clients (n = 17), xylazine emergence was identified at different times, in various ways. Initially, during summer 2022, clients identified a "tranquilizer-like substance" that worsened sedation and withdrawal and caused wounds. SSP medical staff later identified this adulterant as xylazine by treating new medical cases and through diverse information-sharing networks that included professional societies and news sources; however, frontline SSP staff and clients needed additional educational resources about xylazine and its side effects. With limited guidance on how to reduce harm from xylazine, SSP clients altered their drug consumption routes, reduced drug use, and relied on peers' experiences with the drug supply to protect themselves. Some individuals also reported preferring xylazine-adulterated opioids and increasing their drug use, including the use of stimulants to avoid over sedation. CONCLUSIONS: Xylazine's emergence characterizes the current era of unprecedented shifts in the unregulated drug supply. We found that xylazine spurred important behavioral changes among people who use drugs (e.g., transitioning from injecting to smoking). Incorporating these experiences into early drug warning surveillance systems and scaling up drug-checking services and safer smoking supply distribution could help mitigate significant health harms caused by xylazine and other emergent adulterants.
Subject(s)
Needle-Exchange Programs , Substance Abuse, Intravenous , Xylazine , Humans , Adult , Female , Male , Drug Contamination , Middle Aged , Harm ReductionABSTRACT
Glabridin is a widely used product in the cosmetics and pharmaceutical industry, which is generally isolated and purified from Licorice (Glycyrrhiza glabra) extract in industrial production. It has wide clinical applications, but significant toxicity has also been reported. The purity of glabridin raw material is generally between 90% and 98%. We have identified a toxic impurity, glabrene, in the industrial product glabridin. Our investigation using an AB wild-type zebrafish toxicity test showed that glabrene has a significant lethal effect with an LC10 of 2.8 µM. Glabrene induced obvious malformation and disrupted cartilage development in zebrafish larvae. Furthermore, the compound significantly reduced larval mobility and caused damage to brain neural tissues. Metabolic pathway analysis and neurotransmitter quantification via ELISA indicated abnormal activation of the phenylalanine metabolic pathway, resulting in elevated dopamine and acetylcholine levels in vivo. These findings provide insights into the potential risks of glabrene contamination and offer a new reference point for enhancing safety measures and quality controls in licorice-derived products.
Subject(s)
Isoflavones , Phenols , Zebrafish , Animals , Isoflavones/metabolism , Phenols/toxicity , Phenols/metabolism , Glycyrrhiza/chemistry , Metabolomics/methods , Drug Contamination , Larva/drug effects , Larva/metabolism , Phenylalanine/metabolism , Dopamine/metabolismABSTRACT
Nitrosamine compounds pose a significant concern as potential carcinogens, prompting heightened scrutiny from regulatory bodies, particularly regarding their presence in pharmaceuticals. The detection of unacceptable levels of N-nitrosodiethylamine (NDMA) in ranitidine has led to widespread recalls, driving interest in alternative medications such as nizatidine, which shares a similar pharmacological class and is used to treat various gastrointestinal conditions. Despite fewer reports on NDMA levels in nizatidine, its structural similarity to ranitidine, characterized by a tertiary amine, underscores the potential for NDMA formation. Addressing the analytical challenges associated with nitrosamine detection, this study focuses on developing and validating an ultra-high pressure liquid chromatography triple quadrupole mass spectrometry (UHPLC-MS/MS) method for quantifying NDMA in both nizatidine active pharmaceutical ingredients and tablet formulations. Method validation adheres to International Council for Harmonisation recommendations, with a demonstrated linear range of 0.25-100 ng/mL for NDMA, exhibiting excellent linearity (regression coefficient >0.999) and efficient recovery rates ranging from 95.98% to 109.57%. The method shows high sensitivity, with limits of detection and quantification of 0.25 and 0.5 ng/mL, respectively. The developed UHPLC-MS/MS method offers a simple, precise, accurate, and selective approach for monitoring NDMA levels in nizatidine formulations available in Australia, promising enhanced sensitivity and specificity with limits of quantification in the ppb and sub-ppb ranges.
Subject(s)
Carcinogens , Drug Contamination , Nitrosamines , Nizatidine , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Nizatidine/chemistry , Nizatidine/analysis , Nitrosamines/analysis , Nitrosamines/chemistry , Carcinogens/analysis , Carcinogens/chemistry , Limit of Detection , Reproducibility of Results , Diethylnitrosamine/analysis , Diethylnitrosamine/chemistry , Linear Models , Tablets/chemistryABSTRACT
In vitro and in silico tests were used to assess the possible genotoxicity and mutagenicity of five impurities that may be present in levothyroxine, a drug used for thyroid hormone replacement therapy. Neither ToxTree nor VEGA (Virtual Models for evaluating the properties of chemicals within a global architecture) identified cause for concern for any of the impurities. Ames test results (doses up to 1â¯mg per plate), with or without metabolic activation, were negative. The micronucleus test with TK6 (human lymphoblastoid) cells, at doses up to 500 µg/mL, with or without metabolic activation, also gave negative results.
Subject(s)
Micronucleus Tests , Mutagenicity Tests , Thyroxine , Humans , Micronucleus Tests/methods , Mutagenicity Tests/methods , Drug Contamination , Mutagens/toxicity , Cell Line , Salmonella typhimurium/drug effects , Salmonella typhimurium/geneticsABSTRACT
Dolutegravir (DLG) has become a distinctive first-line antiretroviral therapy for the treatment of HIV in most countries due to its affordability, high efficacy, and low drug-drug interactions. However, the evaluation of genotoxic impurities (GTIs) in DLG and their toxicity assessment has not been explored thoroughly. Thus, in this study, a simple, fast, and selective analytical methodology was developed for the identification and determination of 7 GTIs in the comprehensive, explicit route of synthesis for the dolutegravir sodium (DLG-Na) drug. A facile, fast ultrasonication-assisted liquid-liquid extraction procedure was adapted to isolate the GTIs in DLG-Na and then analyzed using the gas chromatography (GC)-electron impact (EI)/mass spectrometer (MS) quantification (using selective ion monitoring mode) technique. This EI-GC/MS method was validated as per the current requirements of ICH Q2 (R1) guidelines. Under optimal method conditions, excellent linearities were achieved with R between 0.9959 and 0.9995, and high sensitivity was obtained in terms of detection limits (LOD) between 0.15 to 0.63 µg/g, and quantification limits (LOQ) between 0.45 to 1.66 µg/g for the seven GTIs in DLG. The obtained recoveries ranged from 98.2 to 104.3 % at LOQ, 15 µg/g, and 18 µg/g concentration levels (maximum daily dose of 100 mg). This developed and validated method is rapid, easy to adopt, specific, sensitive, and accurate in estimating the seven GTIs in a relatively complex sodium matrix of the DLG-Na drug moiety. As a method application, two different manufactured samples of DLG-Na drug substances were analyzed for the fate of the GTIs and drug safety for the intended dosage applications. Moreover, an in-silico QSAR toxicity prediction assessment was carried out to prove scientifically the potential GTI nature of each impurity from the alerting functional groups.
Subject(s)
Drug Contamination , Gas Chromatography-Mass Spectrometry , Heterocyclic Compounds, 3-Ring , Limit of Detection , Oxazines , Piperazines , Pyridones , Heterocyclic Compounds, 3-Ring/chemistry , Heterocyclic Compounds, 3-Ring/analysis , Piperazines/chemistry , Piperazines/analysis , Pyridones/chemistry , Pyridones/analysis , Gas Chromatography-Mass Spectrometry/methods , Oxazines/chemistry , Reproducibility of Results , Linear Models , Mutagens/analysis , Anti-HIV Agents/analysis , Anti-HIV Agents/chemistry , Liquid-Liquid Extraction/methods , Sonication/methods , Computer Simulation , HumansABSTRACT
Methods for the reliable and effective detection and identification of impurities are crucial to ensure the quality and safety of biopharmaceutical products. Technical limitations constrain the accurate identification of individual impurity peaks by size-based electrophoresis separations followed by mass spectrometry. This study presents a size-based electrophoretic method for detecting and identifying impurity peaks in antibody production. A hydrogen sulfide-accelerated degradation method was employed to generate known degradation products observed in bioreactors that forms the basis for size calibration. LabChip GXII channel electrophoresis enabled the rapid (< 1 min) detection of impurity peaks based on size, while capillary zone electrophoresis-mass spectrometry (CZE-MS) facilitated their accurate identification. We combine these techniques to examine impurities resulting from cell culture harvest conditions and forced degradation to assess antibody stability. To mimic cell culture harvest conditions and the impact of forced degradation, we subjected samples to cathepsin at different pH buffers or exposed them to high pH and temperature. Our method demonstrated the feasibility and broad applicability of using a CZE-MS generated spectral library to unambiguously assign peaks in high throughput size-based electrophoresis (i.e., LabChip GXII) with identifications or likely mass of the antibody impurity. Overall, this strategy combines the utility of CZE-MS as a high-resolution separation and detection method for impurities with size-based electrophoresis methods that are typically used to detect (not identify) impurities during the discovery and development of antibody therapeutics.
Subject(s)
Drug Contamination , Electrophoresis, Capillary , Mass Spectrometry , Electrophoresis, Capillary/methods , Mass Spectrometry/methods , Drug Contamination/prevention & control , Animals , CHO Cells , Cricetulus , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/analysis , Hydrogen-Ion Concentration , Cathepsins/analysis , BioreactorsABSTRACT
With increased demand on sealed packed, pre-sterilized ready-to-use (RTU) components like Syringes & Vials, the ebeam technology is used as transfer technology with surface decontamination for transfer of the RTU in a GRADE A environment like an Isolator.
Subject(s)
Sterilization , Syringes , Sterilization/methods , Drug Packaging/methods , Technology, Pharmaceutical/methods , Decontamination/methods , Technology Transfer , Humans , Drug Contamination/prevention & controlABSTRACT
The LAL test has been the "gold standard" for endotoxin testing ever since it was first published as USP Chapter <85> in 1980. Since then, a number of innovative methods have been proposed to augment or replace the LAL test. However novel an alternate test method might be, we must be cognizant of our obligation to patient safety and heed compendial and compliance requirements to demonstrate results equivalence between any candidate (alternate) method and a predicate (compendial) test method. The following discussion explores the concepts of "equivalent", "different" and "not different", proposes the use of a two one sided test (TOST) for the demonstration of equivalence and provides examples of calculations using commercially available software to assess data on alternative endotoxins detection methods that have been published in the public domain1.
Subject(s)
Endotoxins , Endotoxins/analysis , Humans , Limulus Test/methods , Drug Contamination/prevention & control , Software , Reproducibility of ResultsABSTRACT
This research introduces a novel approach for detecting sartan antihypertensive drug adulteration in herbal oral liquids using cotton fiber-supported liquid extraction (CF-SLE) combined with high-performance liquid chromatography-fluorescence detection (HPLC-FLD). Optimal extraction parameters were determined through systematic method development, establishing a sample solution with a pH of 3.0, using 200â¯mg of cotton fiber, ethyl acetate as the extraction solvent, and a solvent volume of 4â¯mL. These conditions demonstrated robust extraction efficiency and were further validated for precision and accuracy, with intra- and inter-day relative standard deviations consistently below 7.5â¯% and relative recoveries ranging from 88.5â¯% to 106.1â¯%. The method exhibited excellent linearity for sartans, with R² values greater than 0.993 across a concentration range of 10-2000â¯ng/mL. Detection limits were effectively established in the range of 2.6-3.1â¯ng/mL, indicating that the method's sensitivity is adequate for the intended screening purposes. This validated method was then applied to real sample analysis, confirming its potential for routine use in detecting illegal additives within complex herbal matrices, thereby ensuring consumer safety and supporting regulatory compliance.
Subject(s)
Cotton Fiber , Drug Contamination , Chromatography, High Pressure Liquid/methods , Cotton Fiber/analysis , Drug Contamination/prevention & control , Limit of Detection , Antihypertensive Agents/analysis , Liquid-Liquid Extraction/methods , Reproducibility of Results , Spectrometry, Fluorescence/methods , Solvents/chemistry , FluorescenceABSTRACT
Pharmaceutical manufacturing utilizes solvents at different stages of production. Some of the harmful solvent residuals may be retained in the final product; therefore, they need to be monitored for quality control and to meet the regulation requirement. Here, a novel method capable of rapidly analyzing residual solvents in pharmaceutical products was developed using a compact-portable gas chromatography with a photoionization detector (GC-PID). The method consists of modified Tedlar® bag sampling, online pre-concentration, separation of volatiles by miniaturized GC, and micro-PID detection. The method detection limits of selected residual solvents were in the range of 26.00 - 52.03â¯pg/mL which is much lower than the pharmaceutical compliance concentration limits. Limits of detection > 520â¯pg of analyte per grams of sample was also determined for the over-the-counter drugs. The method performance showed rapid speed (5â¯min), linear calibration (r2 < 0.99), and repeatable retention time (RSD < 0.4â¯%). Direct analysis of residual solvents in solid samples was conducted without the need for complex sample preparation. The method validation using over-the-counter pharmaceutical products yielded excellent accuracy (recovery > 91.2â¯%) and precision (RSD < 6.5â¯%) for the selected residual solvents, including 1,4-dioxane, benzene, chlorobenzene, cyclohexane, xylenes, and toluene. This portable and rapid method could be deployed during the pharmaceutical drug manufacturing processes for quality control.
Subject(s)
Limit of Detection , Solvents , Solvents/chemistry , Solvents/analysis , Chromatography, Gas/methods , Chromatography, Gas/instrumentation , Drug Contamination/prevention & control , Pharmaceutical Preparations/analysis , Quality Control , Reproducibility of Results , CalibrationABSTRACT
Under the background of digitalization of traditional Chinese medicine (TCM), to realize the quick identification and adulteration analysis of Pulsatilla Radix (PR), adhering to digital conviction, this study conducted UHPLC-QTOF-MSE analysis on PR and its adulterant-Pulsatilla Cernua (PC) from different batches and based on digital conversion, the shared ions were extracted from different batches of PR and PC as their "ions representation", respectively. Further, the data set of unique ions of PR relative to PC and PC relative to PR were screened out as the "digital identities" of PR and PC respectively. Further, above the "digital identities" of PR and PC were used as the benchmarks for matching and identifying to feedback give a matching credibility (MC). The results showed that based on the "digital identities" of PR and PC, the digital identification of two herbal samples can be realized efficiently and accurately at the individual level with the MC≥70.00 %, even if 5 % of PC in the mixed samples can still be identified efficiently and accurately. The study is of great practical significance for improving the identification efficiency of PR and PC, cracking down on adulterated and counterfeit drugs, and strengthening the quality control of PR. In addition, it has important reference significance for developing non-targeted digital identification of herbal medicines at the individual level based on UHPLC-QTOF-MSE and the "digital identity", which was beneficial to the construction of digital Chinese medicine and digital quality control.
Subject(s)
Drug Contamination , Drugs, Chinese Herbal , Pulsatilla , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Pulsatilla/chemistry , Mass Spectrometry/methods , Reproducibility of ResultsABSTRACT
BACKGROUND: Since late 2019, fortification of 'regular' cannabis plant material with synthetic cannabinoid receptor agonists (SCRAs) has become a notable phenomenon on the drug market. As many SCRAs pose a higher health risk than genuine cannabis, recognizing SCRA-adulterated cannabis is important from a harm reduction perspective. However, this is not always an easy task as adulterated cannabis may only be distinguished from genuine cannabis by dedicated, often expensive and time-consuming analytical techniques. In addition, the dynamic nature of the SCRA market renders identification of fortified samples a challenging task. Therefore, we established and applied an in vitro cannabinoid receptor 1 (CB1) activity-based procedure to screen plant material for the presence of SCRAs. METHODS: The assay principle relies on the functional complementation of a split-nanoluciferase following recruitment of ß-arrestin 2 to activated CB1. A straightforward sample preparation, encompassing methanolic extraction and dilution, was optimized for plant matrices, including cannabis, spiked with 5 µg/mg of the SCRA CP55,940. RESULTS: The bioassay successfully detected all samples of a set (n = 24) of analytically confirmed authentic Spice products, additionally providing relevant information on the 'strength' of a preparation and whether different samples may have originated from separate batches or possibly the same production batch. Finally, the methodology was applied to assess the occurrence of SCRA adulteration in a large set (n = 252) of herbal materials collected at an international dance festival. This did not reveal any positives, i.e. there were no samples that yielded a relevant CB1 activation. CONCLUSION: In summary, we established SCRA screening of herbal materials as a new application for the activity-based CB1 bioassay. The simplicity of the sample preparation, the rapid results and the universal character of the bioassay render it an effective and future-proof tool for evaluating herbal materials for the presence of SCRAs, which is relevant in the context of harm reduction.
Subject(s)
Cannabinoid Receptor Agonists , Cannabis , Cannabis/chemistry , Receptor, Cannabinoid, CB1/agonists , Receptor, Cannabinoid, CB1/metabolism , Humans , Drug Contamination , Biological Assay , Cannabinoids/analysisABSTRACT
A quantitative testing method was developed for the analysis of low molecular weight (small molecules) nitrosamine impurities in cough syrups using solid phase extraction (SPE) on strong cation-exchange functionalized polymeric sorbent cartridges followed by gas chromatography-mass spectrometry. The matrix spike recoveries of the nitrosamine impurities from the cough syrup samples was observed to be within the range of 90 %-120 %. Limit of detection (LOD) achieved for NNitrosodimethylamine (NDMA) and NNitroso morpholine (NMOR) was about 0.1 ng/mL while the LOD for NNitrosodiethylamine (NDEA), NNitrosodiisopropylamine (NDIPA) and NNitrosoisopropylethylamine (NIPEA) impurities was about 0.02 ng/mL. The method was evaluated and found to meet the acceptable criteria as per the ICH Q2 guidelines for a working concentration range of 0.02 ng/mL to 1.2 ng/mL for the analyzed impurities. The selectivity of the nitrosamine impurities against the presence of drug product was established using multiple reaction monitoring (MRM) transitions during analysis.
Subject(s)
Antitussive Agents , Drug Contamination , Gas Chromatography-Mass Spectrometry , Limit of Detection , Nitrosamines , Solid Phase Extraction , Nitrosamines/analysis , Solid Phase Extraction/methods , Gas Chromatography-Mass Spectrometry/methods , Antitussive Agents/analysis , Antitussive Agents/chemistry , Reproducibility of ResultsABSTRACT
The pollution of mycotoxins to crops such as traditional Chinese medicines (TCMs) is an established problem throughout the world. Thus, mycotoxin determination in TCMs during production and processing is significantly necessary, which means rapid, sensitive and accurate analytical methods are needed. In this work, a new method of visual protein microarray based on a 96-well microtiter plate was proposed. Combined with a colorimetric method, five mycotoxins (ochratoxin A, zearalenone, deoxynivalenol, aflatoxin B1 and fumonisin B1) in 90 samples (TCMs) could be detected simultaneously within 30â¯minutes. The detection limits for the five mycotoxins are 0.25⯵g/kg, 0.33⯵g/kg, 11.84⯵g/kg, 0.06⯵g/kg, and 3.58⯵g/kg, which can satisfy specified requirements of mycotoxins in the Chinese Pharmacopoeia (2020 edition) adequately. Under repeated conditions, experiments were carried out on actual samples to verify the feasibility of the method. The results showed that the recoveries of all analytes were between 70â¯% and 120â¯%, and the relative standard deviations were less than 15â¯%. In comparison to LC-MS/MS, this method significantly reduces the required time, and the colorimetric technique offers more direct results compared to fluorescence-based screening assays. This method exhibits substantial potential for the rapid and sensitive on-site detection of TCMs for quality control.
Subject(s)
Colorimetry , Drug Contamination , Drugs, Chinese Herbal , Limit of Detection , Mycotoxins , Protein Array Analysis , Mycotoxins/analysis , Protein Array Analysis/methods , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/chemistry , Drug Contamination/prevention & control , Colorimetry/methods , Medicine, Chinese Traditional , Tandem Mass Spectrometry/methodsABSTRACT
In this study we analyzed drug recall data from the U.S. Food and Drug Administration (FDA) over the period 2012-2023. We identified trends in the number of recalls initiated annually and their underlying causes. On average, 330 drug recalls are initiated each year, showing an overall increasing trend. The average duration of a recall, from initiation to termination date, was 1.3 years and each recall involved on average 400 000 product units, implying considerable resource demands and consequences for all stakeholders. The most frequent cause of these recalls was found to be impurities and contaminants (37â¯%), followed by control (28â¯%) and labeling/packaging (19â¯%) issues. Recalls of medicines causing serious health problems or death (class I), accounted for 14â¯% of the recall events. Continuous evaluation of recalls is expected to reduce their number, mitigate their impact on the healthcare system and improve drug safety.
Subject(s)
Drug Recalls , United States Food and Drug Administration , United States , Drug Contamination , Humans , Drug Labeling/standards , Data Analysis , Pharmaceutical Preparations/analysisABSTRACT
AIMS: To investigate an in-line Raman method capable of detecting accidental microbial contamination in pharmaceutical vessels, such as bioreactors producing monoclonal antibodies via cell culture. METHODS AND RESULTS: The Raman method consists of a multivariate model built from Raman spectra collected in-line during reduced-scale bioreactor batches producing a monoclonal antibody, as well as a reduced-scale process with intentional spiking of representative compendial method microorganisms (n = 4). The orthogonal partial least squares regression discriminant analysis model (OPLS-DA) area under the curve (AUC), specificity and sensitivity were 0.96, 0.99, and 0.95, respectively. Furthermore, the model successfully detected contamination in an accidentally contaminated manufacturing-scale batch. In all cases, the time to detection (TTD) for Raman was superior compared to offline, traditional microbiological culturing. CONCLUSIONS: The Raman OPLS-DA method met acceptance criteria for equivalent decision making to be considered a viable alternative to the compendial method for in-process bioburden testing. The in-line method is automated, non-destructive, and provides a continuous assessment of bioburden compared to an offline compendial method, which is manual, results in loss of product, and in practice is only collected once daily and requires 3-5 days for enumeration.
Subject(s)
Antibodies, Monoclonal , Bioreactors , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Bioreactors/microbiology , Drug Contamination/prevention & control , Bacteria/isolation & purificationABSTRACT
Reduced glutathione (GSH) is an endogenous tripeptide antioxidant which plays a crucial role in a variety of physiological and pathological activities. Although GSH is not present in any FDA-approved drug product, GSH dietary supplement products and compounded GSH drugs are available to patients in the US. Several incidents of toxicity have occurred in recent years due to endotoxin or otherwise contaminated GSH in compounded drugs. Efficient and sensitive analytical methods are needed for assessing and ensuring the quality of GSH substance and associated drug or dietary supplement products. Impurities A (L-cysteinylglycine), B (cysteine), C (oxidized L-glutathione) and D (γ-L-glutamyl-L-cysteine) are the main related impurities for GSH drug substance which have been detected and quantified by capillary electrophoresis and qNMR analytical procedures. However, there are no reported HPLC methods for detecting or quantifying the three main related impurities A, B and D even though numerous HPLC analytical methods have been reported for analyzing GSH and impurity C. In this report, an isocratic HPLC-UV analytical procedure was developed and validated for separating and identifying GSH and related impurities A-D as well as a newly identified degradant, L-pyroglutamic acid (pGlu), within 10â¯minutes with resolution (RS) more than 3. The LOD and LOQ were determined to be 0.02â¯% w/w and 0.05â¯% w/w, respectively, for impurities A-D and pGlu. Importantly, the optimized HPLC analytical procedure for GSH assay does not have interference from impurities A, B and D, providing highly specific results compared to the commonly used iodine titration method. The newly validated analytical procedure was applied to assess different commercial GSH bulk substance samples. The results suggest that the analytical procedure described in this work is suitable for quality assessment of GSH samples.
Subject(s)
Drug Contamination , Glutathione , Glutathione/analysis , Chromatography, High Pressure Liquid/methods , Drug Contamination/prevention & control , Dipeptides/analysis , Dipeptides/chemistry , Dietary Supplements/analysis , Reproducibility of Results , Spectrophotometry, Ultraviolet/methods , Cysteine/analysis , Cysteine/chemistry , Pyrrolidonecarboxylic Acid/analysis , Pyrrolidonecarboxylic Acid/chemistry , Limit of DetectionABSTRACT
Etimicin is a typical aminoglycoside antibiotic (AG). High performance liquid chromatography-evaporation light scattering detector (HPLC-ELSD) method is a commonly used method for determining impurities in Etimicin. However, due to the poor reproducibility, low sensitivity and narrow linear range of the ELSD, high-throughput quantitative analysis of impurities in Etimicin currently poses a challenge. In this study, a sensitive method using hydrophilic interaction liquid chromatography coupled with charged aerosol detector (HILIC-CAD) was developed for the analysis of the impurities in Etimicin. The liquid phase conditions for determination impurities in Etimicin were optimized using Box Behnken design (BBD) and response surface methodology (RSM), resulting in satisfactory separation and optimal CAD output signal. We also studied the influence of CAD parameters on the signal-to-noise ratio and linearity of Etimicin and its impurities. This method has also been proven to be effective in separating impurities from two other typical AGs, Isepamicin and Amikacin. In the method validation, the coefficient of determination (R2) of Etimicin, Isepamicin and Amikacin and their impurities were all greater than 0.999, within the range of 0.5-50 µg/mL. The average recoveries of the impurities of three typical AGs were 99.03â¯%-101.22â¯%, RSDs all were less than 2.5â¯% for intra-day and inter-day precision, with good precision and accuracy. The developed HILIC-CAD quantification method was sensitive, accurate and highly selective for quantitative analysis of impurities in the AGs without need ion-pairing reagents, which is ensure the public medication safety. The method is first reported application of HILIC-CAD method for quantitative analysis of the impurities in AGs.
Subject(s)
Aerosols , Drug Contamination , Hydrophobic and Hydrophilic Interactions , Aerosols/analysis , Aerosols/chemistry , Drug Contamination/prevention & control , Chromatography, High Pressure Liquid/methods , Reproducibility of Results , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Amikacin/analysis , Amikacin/chemistry , Limit of Detection , Signal-To-Noise Ratio , AminoglycosidesABSTRACT
A simple and sensitive fluorescent probe has been developed and optimized to detect the non-intentional administration of levamisole (LVM). LVM is used as an anthelmintic therapy in cows, and hence, its residues appear in the drained milk until 60 hours after administering the drug. Meanwhile, levamisole is known to be an adulterant to cocaine and could be detected in addicts' plasma samples. Owing to its severe side effects, including agranulocytosis, which is lethal in many cases, detection and quantification of LVM in milk and plasma samples are of utmost importance. Therefore, a sensitive and selective analytical method is required for this purpose. This work develops a highly fluorescent probe obtained through the reaction between LVM and erythrosine-B in an acidic medium, where the produced ion pair complex has been measured at 553 nm after excitation at 528 nm. The proposed method provides linearity over the concentration range of 0.5-2.0 µg mL-1 for LVM, with a corresponding detection and quantitation limit of 0.5 and 0.3 µg mL-1. Full validation was performed, permitting the application of the suggested method to perform simple extraction steps. All the applied procedures followed the guidelines offered by green analytical chemistry, where the Green Analytical Procedure Index (GAPI) assessed the greenness of the proposed tool, and the yielded pictograms proved the eco-friendliness of the offered tool.