Selective detection of azelnidipine in pharmaceuticals via carbon dot mediated spectrofluorimetric method: A green approach.

A spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N-doped CDs (N-CDs) were synthesized through a single-step hydrothermal process, using citric acid and urea as precursor materials. The prepared N-CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N-CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV-vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N-CDs and AZEL, leading to fluorescence quenching of N-CDs as a result of ground-state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10-200 µg/ml (R2 = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the 'Analytical GREEnness (AGREE)' scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL.

For the occurrence of PPCPs from source to tap: A novel approach modified in terms of sample preservation and SPE cartridge to monitor PPCPs in our water supply.

BACKGROUND: The ongoing infusion of pharmaceutical and personal care products (PPCPs) into ecosystems sustains a perpetual life cycle and leads to multi-generational exposures. Limited understanding of their environmental impact and their intrinsic ability to induce physiological effect in humans, even at low doses, pose great risks to human health. Few scholarly works have conducted systematic research into the occurrence of PPCPs within potable water systems. Concurrently, the associated monitoring techniques have not been comprehensively examined with regards to the specific nature of drinking water, namely whether the significant presence of disinfectants may influence the detection of PPCPs. RESULTS: A modified approach in terms of detailed investigation of sample preservation and optimization of an in-lab fabricated solid phase extraction (SPE) cartridge filled with DVB-VP and PS-DVB sorbent was proposed. Favorable methodological parameters were achieved, with correlation coefficients spanning from 0.9866 to 0.9998. The LODs of the PPCPs fluctuated from 0.001 to 2 µg L-1, while the LOQs varied from 0.002 to 5 µg L-1. The analysis of spiked samples disclosed a methodological precision of 2.31-9.86 % and a recovery of 52.4-119 %. We utilized the established method for analyzing 14 water samples of three categories (source water, finished water and tap water) from five centralized water supply plants. A total of 24 categories encompassing 72 PPCPs were detected, with the concentrations of PPCPs manifested a marked decrease from source water to finished water and finally to tap water. SIGNIFICANCE: Our research meticulously examined the enhancement and purification effects of widely used commercial SPE cartridges and suggested the use of in-lab fabricated SPE cartridges packed with DVB-VP and PS-DVB adsorbents. We also conducted a systematic evaluation of the need to incorporate ascorbic acid and sodium thiosulfate as preservatives for PPCP measurement, in consideration of the unique characteristics of drinking water matrices, specifically, the significant concentration levels of disinfectants. Furthermore, the proposed method was effectively employed to study the presence of PPCPs in source water, finished water, and tap water collected from centralized water supply plants.

A culture-independent nucleic acid diagnostics method for use in the detection and quantification of Burkholderia cepacia complex contamination in aqueous finished pharmaceutical products.

The Burkholderia cepacia complex (Bcc) is the number one bacterial complex associated with contaminated Finished Pharmaceutical Products (FPPs). This has resulted in multiple healthcare related infection morbidity and mortality events in conjunction with significant FPP recalls globally. Current microbiological quality control of FPPs before release for distribution depends on lengthy, laborious, non-specific, traditional culture-dependent methods which lack sensitivity. Here, we present the development of a culture-independent Bcc Nucleic Acid Diagnostic (NAD) method for detecting Bcc contaminants associated with Over-The-Counter aqueous FPPs. The culture-independent Bcc NAD method was validated to be specific for detecting Bcc at different contamination levels from spiked aqueous FPPs. The accuracy in Bcc quantitative measurements was achieved by the high degree of Bcc recovery from aqueous FPPs. The low variation observed between several repeated Bcc quantitative measurements further demonstrated the precision of Bcc quantification in FPPs. The robustness of the culture-independent Bcc NAD method was determined when its accuracy and precision were not significantly affected during testing of numerous aqueous FPP types with different ingredient matrices, antimicrobial preservative components and routes of administration. The culture-independent Bcc NAD method showed an ability to detect Bcc in spiked aqueous FPPs at a concentration of 20 Bcc CFU/mL. The rapid (≤ 4 hours from sample in to result out), robust, culture-independent Bcc NAD method presented provides rigorous test specificity, accuracy, precision, and sensitivity. This method, validated with equivalence to ISO standard ISO/TS 12869:2019, can be a valuable diagnostic tool in supporting microbiological quality control procedures to aid the pharmaceutical industry in preventing Bcc contamination of aqueous FPPs for consumer safety.

Solid-phase microextraction - a future technique in pharmacology and coating trends.

Traditional sample preparation techniques based on liquid-liquid extraction (LLE) or solid-phase extraction (SPE) often suffer from a major error due to the matrix effects caused by significant co-extraction of matrix components. The implementation of a modern extraction technique such as solid-phase microextraction (SPME) was aimed at reducing analysis time and the use of organic solvents, as well as eliminating pre-analytical and analytical errors. Solid-phase microextraction (SPME) is an innovative technique for extracting low molecular weight compounds (less than 1500 Da) from highly complex matrices, including biological matrices. It has a wide range of applications in various types of analysis including pharmaceutical, clinical, metabolomics and proteomics. SPME has a number of advantages over other extraction techniques. Among the most important are low environmental impact, the ability to sample and preconcentrate analytes in one step, simple automation, and the ability to extract multiple analytes simultaneously. It is expected to become, in the future, another method for cell cycle research. Numerous available literature sources prove that solid-phase microextraction can be a future technique in many scientific fields, including pharmaceutical sciences. This paper provides a literature review of trends in SPME coatings and pharmacological applications.

Removal of pharmaceutical compounds and toxicology study in wastewater using Malaysian fungal Ganoderma lucidum.

Elevated usage of pharmaceutical products leads to the accumulation of emerging contaminants in sewage. In the current work, Ganoderma lucidum (GL) was used to remove pharmaceutical compounds (PCs), proposed as a tertiary method in sewage treatment plants (STPs). The PCs consisted of a group of painkillers (ketoprofen, diclofenac, and dexamethasone), psychiatrists (carbamazepine, venlafaxine, and citalopram), beta-blockers (atenolol, metoprolol, and propranolol), and anti-hypertensives (losartan and valsartan). The performance of 800 mL of synthetic water, effluent STP, and hospital wastewater (HWW) was evaluated. Parameters, including treatment time, inoculum volume, and mechanical agitation speed, have been tested. The toxicity of the GL after treatment is being studied based on exposure levels to zebrafish embryos (ZFET) and the morphology of the GL has been observed via Field Emission Scanning Electron Microscopy (FESEM). The findings conclude that GL can reduce PCs from <10% to >90%. Diclofenac and valsartan are the highest (>90%) in the synthetic model, while citalopram and propranolol (>80%) are in the real wastewater. GL effectively removed pollutants in 48 h, 1% of the inoculum volume, and 50 rpm. The ZFET showed GL is non-toxic (LC50 is 209.95 mg/mL). In the morphology observation, pellets GL do not show major differences after treatment, showing potential to be used for a longer treatment time and to be re-useable in the system. GL offers advantages to removing PCs in water due to their non-specific extracellular enzymes that allow for the biodegradation of PCs and indicates a good potential in real-world applications as a favourable alternative treatment.

Unveiling the potential of machine learning in cost-effective degradation of pharmaceutically active compounds: A stirred photo-reactor study.

In this study, neural networks and support vector regression (SVR) were employed to predict the degradation over three pharmaceutically active compounds (PhACs): Ibuprofen (IBP), diclofenac (DCF), and caffeine (CAF) within a stirred reactor featuring a flotation cell with two non-concentric ultraviolet lamps. A total of 438 datapoints were collected from published works and distributed into 70% training and 30% test datasets while cross-validation was utilized to assess the training reliability. The models incorporated 15 input variables concerning reaction kinetics, molecular properties, hydrodynamic information, presence of radiation, and catalytic properties. It was observed that the Support Vector Regression (SVR) presented a poor performance as the ε hyperparameter ignored large error over low concentration levels. Meanwhile, the Artificial Neural Networks (ANN) model was able to provide rough estimations on the expected degradation of the pollutants without requiring information regarding reaction rate constants. The multi-objective optimization analysis suggested a leading role due to ozone kinetic for a rapid degradation of the contaminants and most of the results required intensification with hydrogen peroxide and Fenton process. Although both models were affected by accuracy limitations, this work provided a lightweight model to evaluate different Advanced Oxidation Processes (AOPs) by providing general information regarding the process operational conditions as well as know molecular and catalytic properties.

Rapid screening of drugs in environmental water using metal organic framework/Ti3C2Tx composite coated blade spray-mass spectrometry.

Simultaneous rapid screening of multiple drugs of abuse in environmental water facilitates effective monitoring and trend assessments. Herein, a novel porphyrin-based metal organic frameworks modified Ti3C2Tx nanosheets (Cu-TCPP/Ti3C2Tx) composite was prepared and utilized as solid-phase microextraction (SPME) coating for the simultaneous analysis of 21 drugs from water samples. The composite was embedded with matrix-compatible polyacrylonitrile binder to prepare a coated blade with thin and uniform coating layer. Ambient mass spectrometry (MS) technique was used to create a coated blade spray-MS (CBS-MS) method for the quantitative determination of drugs in water samples. High throughput and automated sample preparation were achieved with the use of a Concept 96-well plate system, enabling analysis of 21 drugs of abuse within 1 min per sample, while using only 8 µL of organic solvent for desorption and CBS-MS detection. The developed method showed favorable linearity (R2 ≥ 0.9983) in the range of 0.05 to 10 ng mL-1, low limits of detection (1.5-9.0 ng L-1), sufficient recovery (67.6-133.2%), as well as satisfactory precision (RSDs≤13.5%). This study not only delivers a novel and efficient SPME coating composite, but also demonstrates the excellent performance of a high-throughput, efficient, and green analytical method for determination of drugs in environmental water.

NMR Longitudinal Rotating Frame Relaxation Time (T1ρ) with a Weak Spin Locking Field as an Approach to Characterize Solid-State Active Pharmaceutical Ingredients: Proof of Concept.

Nuclear magnetic resonance (NMR) longitudinal rotating frame relaxation time (T1ρ), rarely used in low-field NMR, can be more effective than conventional T1 and T2 relaxation times to differentiate polymorphic forms of solid pharmaceuticals. This could be attributed to T1ρ sensibility to structural and molecular dynamics that can be enhanced by changing the strength of the oscillating magnetic field (B1) of spinlock pulses. Here, we compared the capacity of T1, T2, and T1ρ to differentiate inactive (A) and active (C) crystalline forms of the World Health Organization essential drug Mebendazole. The results showed that T1 and T2 values of both forms were statistically identical at 0.47 T. Conversely, T1ρ of both forms measured with weak spinlock B1 fields, ranging from 0.08 to 0.80 mT were statistically different in the same spectrometer. The T1ρ also has the limit of detection to detect the presence of at least 10% of inactive A form in the active C form. Therefore, T1ρ, measured with weak spinlock B1 fields can be an effective, streamlined, and complementary approach for characterizing not only solid active pharmaceutical ingredients but other solid-state materials as well.

Occurrence of pharmaceutically active compounds in groundwater and their effects to the human health.

Groundwater contamination by pharmaceutically active compounds (PhACs) has been considered a public health concern worldwide. Alongside the potential toxicological risk of these organic substances, many countries still rely on groundwater for drinking water supply. Thus, this study identified a priority list of seven licit PhACs, comprising acetaminophen (ACT), tramadol (TRA), carbamazepine (CBZ), erythromycin (ERY), sulfamethoxazole (SMX), metformin (MET), and oxazepam (OXZ). Consumption, concentration, and human toxicity in silico results were collected from open access databases. These three indicators were analyzed separately and grouped through a general risk index. The consumption index (data from the USA and Brazil) indicated that ACT, TRA, and MET are the most consumed. Monitoring samples from the USA and Europe (n = 816) indicated that OXZ and ERY stand out as the higher occurrence index considering both regions, but the ranking for each region showed considerable differences. When assessing toxicological risk, an index ≥ 0.5 was attributed to CBZ, MET, OXZ, SMX, and TRA. The general risk indicated the need to be attentive to MET, OXZ, and TRA as they presented ≥ 0.5 index values for at least two indicators.

Emerging contaminants as unintentional substances in paper and board: A case of unexpected pharmaceuticals detection in the paper recycling chain.

The contamination of paper products by various chemicals has been reported on a global level, but to date, no published research has investigated pharmaceutical contamination of paper-based products. In this study, pharmaceutical analysis was conducted on 42 samples collected from various points of the recycled paper value chain in Cape Town, South Africa, which included the various grades that may be included in the manufacturing of recycled paperboard. The analysis was achieved by ultrasonic-assisted extraction of paper samples before detection by UHPLC-Q Orbitrap. Quantification limits ranged from 1.15 pg/g for ketoprofen to 46.07 pg/g for methocarbamol. Pharmaceuticals identified in newspaper samples were dexamethasone, ketoprofen, and 17ß-estradiol. The latter was also detected in paper shopping bags (up to 697.49 ng/g), infant bathtub packaging (280.62 ng/g), battery packaging (137.43 ng/g), and an egg carton (170.47 ng/g). Carbamazepine was also prominent with its concentration reaching 13.02 ng/g in a vegetable box. Suspect screening tentatively identified 14 additional pharmaceuticals in paper samples, with minocycline, prazepam, and anabolic steroids appearing more prominently. This pioneering study indicated that unintentional pharmaceutical exposure had expanded beyond environmental media to consumer products.

A sustainable sensitive spectrofluorimetric approach for the determination of the multipotent protein lactoferrin in different pharmaceuticals and infant milk formula: Compliance with greenness metrics.

The current study presents the first spectrofluorimetric approach for the estimation of lactoferrin, depending on the measurement of its native fluorescence at 337 nm after excitation at 230 nm, without the need for any hazardous chemicals or reagents. It was found that the fluorescence intensity versus concentration calibration plot was linear over the concentration range of 0.1-10.0 µg/mL with quantitation and detection limits of 0.082 and 0.027 µg/mL, respectively. The method was accordingly validated according to the ICH recommendations. The developed method was applied for the estimation of lactoferrin in different dosage forms, including capsules and sachets with high percent recoveries (97.84-102.53) and low %RSD values (<1.95). Lactoferrin is one of the key nutrients in milk powder and a significant nutritional fortifier. In order to assess the quality of milk powder, it is essential to rapidly and accurately quantify the lactoferrin content of the product. Therefore, the presented study was successfully applied for the selective estimation of lactoferrin in milk powder with acceptable percent recoveries (96.45-104.92) and %RSD values (≤3.607). Finally, the green profile of the method was estimated using two assessment tools: Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE), which demonstrated its excellent greenness.

Innovative Solid-Phase Extraction Strategies for Improving the Advanced Chromatographic Determination of Drugs in Challenging Biological Samples.

In the past few decades, considerable scientific strides have been made in the subject of drug analysis in human biological samples. However, the risk caused by incorrect drug plasma levels in patients still remains an important concern. This review paper attempts to investigate the advances made over the last ten years in common sample preparation techniques (SPT) for biological samples based on solid sorbents, including solid-phase extraction (SPE) and solid-phase micro-extraction (SPME), and in particular in the field of molecularly imprinted polymers (MIPs), including non-stimuli-responsive and stimuli-responsive adsorbents. This class of materials is known as 'smart adsorbents', exhibiting tailored responses to various stimuli such as magnetic fields, pH, temperature, and light. Details are provided on how these advanced SPT are changing the landscape of modern drug analysis in their coupling with liquid chromatography-mass spectrometry (LC-MS) analytical techniques, a general term that includes high-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography (UHPLC), as well as any variation of MS, such as tandem (MS/MS), multiple-stage (MSn), and high-resolution (HRMS) mass spectrometry. Some notes are also provided on coupling with less-performing techniques, such as high-performance liquid chromatography with ultraviolet (HPLC-UV) and diode array detection (HPLC-DAD) detection. Finally, we provide a general review of the difficulties and benefits of the proposed approaches and the future prospects of this research area.

A picture of pharmaceutical pollution in landfill leachates: Occurrence, regional differences and influencing factors.

Municipal solid waste (MSW) landfill sites have been identified as a significant source of pharmaceuticals in the environment because unused or expired pharmaceuticals are discarded into MSW, which eventually percolate into leachates. However, the contamination of pharmaceuticals in landfill leachate in China is not comprehensively understood. Previous research into factors influencing pharmaceutical concentrations focused on a limited number and type of target pollutants or restricted study area. In the present study, 66 pharmaceuticals were analyzed (including 45 antibiotic and 21 non-antibiotic pharmaceuticals, also categorized as 59 prescription and 7 non-prescription pharmaceuticals) in leachate samples from landfill sites with various characteristics in different regions of China. The results indicated that non-antibiotic pollutants were present at significantly higher concentrations than antibiotic pollutants, with median concentrations of 1.74 µg/L and 527 ng/L, respectively. Non-antibiotic pollutants also presented a higher environmental risk than antibiotic pollutants, by 2 to 4 orders of magnitude, highlighting that non-antibiotic pharmaceuticals should not be overlooked during the assessment of landfill leachate. Pharmaceutical concentrations in landfill leachate samples exhibited regional differences; the population size served by the landfills was the dominant factor contributing to the observed differences. In addition, landfill characteristics such as the solid waste composition and MSW loading can also affect pharmaceutical concentrations in landfill leachate. Despite the implementation of the classification and disposal policy of MSW in Shanghai, China since July 2019, specifying that unused or expired pharmaceuticals should be discarded as hazardous waste, high levels of pharmaceutical contaminations were detected in leachate from the main components of classified MSW (i.e., residual and food waste). These findings emphasize the importance of pharmaceutical management in solid waste systems.

Crystallization and Solvent Evaporation Ionization Mass Spectrometry (CSEI-MS) for Rapid Detection of Drugs in Complex Matrices.

Illegal addition of drugs is common but seriously threatens public health safety. Conventional mass spectrometry methods are difficult to realize direct analysis of drugs existing in some complex matrices such as seawater or soil due to the ion suppression effect and contamination to MS parts caused by nonvolatile salts. In this work, a novel crystallization and solvent evaporation ionization mass spectrometry (CSEI-MS) method was constructed and developed to achieve rapid desalting detection. CSEI only consists of a heated plate and a nebulizer and exhibits excellent desalting performance, enabling direct analysis of six drugs dissolved in eight kinds of salt solutions (up to 200 mmol/L) and three complex salty matrices. Under optimized conditions, CSEI-MS presents high sensitivity, accuracy, linearity, and intraday and interday precision. Finally, this method is applied to the quantitative analysis of drugs in seawater, hand cream, and soil. Furthermore, the highly sensitive detection of CSEI-MS is demonstrated to remain even if the detection processes are conducted within 5 s via common commercial tools.

A Novel Low-Frequency Electromagnetic Active Inertial Sensor for Drug Detection.

The purpose of this paper is to demonstrate a new discovery regarding the interaction between materials and very low radio frequencies. Specifically, we observed a feedback response on an inertia active sensor when specific frequencies (around 2-4 kHz) are used to irradiate targeted pharmaceutical samples like aspirin or paracetamol drugs. The characteristics of this phenomenon, such as excitation and relaxation time, the relation between deceleration and a material's quantity, and signal amplitude, are presented and analyzed. Although the underlying physics of this phenomenon is not yet known, we have shown that it has potential applications in remote identification of compounds, detection, and location sensing, as well as identifying substances that exist in plants without the need for any processing. This method is fast, accurate, low-cost, non-destructive, and non-invasive, making it a valuable area for further research that could yield spectacular results in the future.

Application of in vitro bioassays to monitor pharmaceuticals in water: A synthesis of chronological analysis, mode of action, and practical insights.

Pharmaceutical compounds in wastewater have emerged as a significant concern for the aquatic environment. The use of in vitro bioassays represents a sustainable and cost-effective approach for assessing the potential toxicological risks of these biologically active compounds in wastewater and aligns with ethical considerations in research. It facilitates high-throughput analysis, captures mixture effects, integrates impacts of both known and unknown chemicals, and reduces reliance on animal testing. The core aim of the current review was to explore the practical application of in vitro bioassays in evaluating the environmental impacts of pharmaceuticals in wastewater. This comprehensive review strives to achieve several key objectives. First, it provides a summary categorisation of pharmaceuticals based on their mode of action, providing a structured framework for understanding their ecological significance. Second, a chronological analysis of pharmaceutical research aims to document their prevalence and trends over time, shedding light on evolving environmental challenges. Third, the review critically analyses existing bioassay applications in wastewater, while also examining bioassay coverage of representative compounds within major pharmaceutical classes. Finally, it explores the potential for developing innovative bioassays tailored for water quality monitoring of pharmaceuticals, paving the way for more robust environmental monitoring and risk assessment. Overall, adopting effect-based methods for pharmaceutical monitoring in water holds significant promise. It encompasses a broad spectrum of biological impacts, promotes standardized protocols, and supports a bioassay test battery approach indicative of different endpoints, thereby enhancing the effectiveness of environmental risk assessment.

Determination of genotoxic impurities of aromatic aldehydes in pharmaceutical preparations by high performance liquid chromatography after derivatization with N-Cyclohexyl-4-hydrazino-1,8-naphthalenediimide.

The detection of aromatic aldehydes, considered potential genotoxic impurities, holds significant importance during drug development and production. Current analytical methods necessitate complex pre-treatment processes and exhibit insufficient specificity and sensitivity. This study presents the utilization of naphthalenediimide as a pre-column derivatisation reagent to detect aromatic aldehyde impurities in pharmaceuticals via high-performance liquid chromatography (HPLC). We screened a series of derivatisation reagents through density functional theory (DFT) and investigated the phenomenon of photoinduced electron transfer (PET) for both the derivatisation reagents and the resulting products. Optimal experimental conditions for derivatisation were achieved at 40 °C for 60 min. This approach has been successfully applied to detect residual aromatic aldehyde genotoxic impurities in various pharmaceutical preparations, including 4-Nitrobenzaldehyde, 2-Nitrobenzaldehyde, 1,4-Benzodioxane-6-aldehyde, and 5-Hydroxymethylfurfural. The pre-column derivatisation method significantly enhanced detection sensitivity and reduced the limit of detection (LOD), which ranged from 0.002 to 0.008 µg/ml for the analytes, with relative standard deviations < 3 %. The correlation coefficient (R2) >0.998 demonstrated high quality. In chloramphenicol eye drops, the concentration of 4-Nitrobenzaldehyde was measured to be 8.6 µg/mL below the specified concentration, with recoveries ranging from 90.0 % to 119.2 %. In comparison to existing methods, our work simplifies the pretreatment process, enhances the sensitivity and specificity of the analysis, and offers comprehensive insights into impurity detection in pharmaceutical preparations.

Improved assay development of pharmaceutical modalities using feedback-controlled liquid chromatography optimization.

Development of meaningful and reliable analytical assays in the (bio)pharmaceutical industry can often be challenging, involving tedious trial and error experimentation. In this work, an automated analytical workflow using an AI-based algorithm for streamlined method development and optimization is presented. Chromatographic methods are developed and optimized from start to finish by a feedback-controlled modeling approach using readily available LC instrumentation and software technologies, bypassing manual user intervention. With the use of such tools, the time requirement of the analyst is drastically minimized in the development of a method. Herein key insights on chromatography system control, automatic optimization of mobile phase conditions, and final separation landscape for challenging multicomponent mixtures are presented (e.g., small molecules drug, peptides, proteins, and vaccine products) showcased by a detailed comparison of a chiral method development process. The work presented here illustrates the power of modern chromatography instrumentation and AI-based software to accelerate the development and deployment of new separation assays across (bio)pharmaceutical modalities while yielding substantial cost-savings, method robustness, and fast analytical turnaround.

Deep eutectic solvents as green and sustainable diluents in headspace gas chromatography for the determination of trace level genotoxic impurities in pharmaceuticals.

Genotoxic impurities (GTIs) are potential carcinogens that need to be controlled down to ppm or lower concentration levels in pharmaceuticals under strict regulations. The static headspace gas chromatography (HS-GC) coupled with electron capture detection (ECD) is an effective approach to monitor halogenated and nitroaromatic genotoxins. Deep eutectic solvents (DESs) possess tunable physico-chemical properties and low vapor pressure for HS-GC methods. In this study, zwitterionic and non-ionic DESs have been used for the first time to develop and validate a sensitive analytical method for the analysis of 24 genotoxins at sub-ppm concentrations. Compared to non-ionic diluents, zwitterionic DESs produced exceptional analytical performance and the betaine : 7 (1,4- butane diol) DES outperformed the betaine : 5 (1,4-butane diol) DES. Limits of detection (LOD) down to the 5-ppb concentration level were achieved in DESs. Wide linear ranges spanning over 5 orders of magnitude (0.005-100 µg g-1) were obtained for most analytes with exceptional sensitivities and high precision. The method accuracy and precision were validated using 3 commercially available drug substances and excellent recoveries were obtained. This study broadens the applicability of HS-GC in the determination of less volatile GTIs by establishing DESs as viable diluent substitutes for organic solvents in routine pharmaceutical analysis.