[Validation Study on Developed Methods for Anions and Bromic Acid in Various Mineral Waters by Ion Chromatography].

Five kinds of anions namely fluoride, chlorate, chlorite, nitrate and nitrite ions, and bromic acid were determined in various mineral waters (MWs), and the methods were validated. MWs are varying in the degree of hardness and contents of carbonate. When the five anions were measured based on the official method of tap water, the peak shape of fluoride ion in MWs with high degree of hardness was different from the standard solution, making it difficult to determine. The same phenomenon was also observed when bromic acid was measured. In order to achieve accurate determination, five-fold dilution with ultrapure water was carried out on the samples. With the additional step, the abnormal peak of both analytes was improved, and no difference in the retention times between standard and sample solutions was observed. The validation tests were performed using the developed methods with the additional diluting step, and the results of all target substances met the criteria of the guideline on analytical method validation for MW in Japan. Our results suggested that the methods we developed could be useful for the accurate determination of the anions and bromic acid in various MWs on the market.

Radiostrontium determination by combination of automated Sr isolation and "on-column" Cherenkov detection using chromatographic model.

A novel analytical solution of non-linear chromatography in case of parabolic isotherm for frontal analysis was obtained by combination of Cole-Hopf and Laplace transform. It was used for simulation of strontium capturing on chromatographic column with aim to improve quantitative determination of low-level 90Sr activities. From the experimentally determined breakthrough curves, the retention factor and the number of theoretical plates were calculated using the Glueckauf and Wenzel relations and by fitting the breakthrough curves for the linear isotherm using MatLab. These were used to simulate the breakthrough curves using a parabolic isotherm solution where the non-linear term of the isotherm was taken as a small negative deviation of the retention factor. On the base of theoretical prediction and experimental data, procedure for automated capturing of strontium on chromatographic column with specific dimension and off line "on-column" Cherenkov detection on commercial ultra low-level liquid scintillation counter was developed. It was shown that analytical solution for parabolic isotherm in comparison with solution for linear isotherm gives better prediction of mass of captured Sr on column filled with small amount of Sr resin and SuperLig®620 in case of elevated Sr concentration, even when non-linear effect is not obvious. The solution also makes it possible to predict the mass of resin required for strontium isolation at 100% yield under given conditions. Considering the limited dimensions of the column, and consequently small mass of the resin in them, it resulted in the low efficiency of the columns, which, however, did not affect the yield in real conditions of isolation. The results have shown that the yields achieved after isolation on SuperLig®620 from real samples are 100%. In addition, it is shown that captured 90Sr can be detected through 90Y ingrowth, on column filled with strontium specific resin, with Cherenkov detection efficiency of at least 50%. The efficiency may be enhanced to 60%, depending on parameters which can affect detection efficiency change (type of column, resin type, surrounding solution, etc.). The developed procedures enable quantitative determination of 90Sr in natural water samples with MDAC below 12 mBq l-1 and solid (soil and vegetation) samples with MDAC below 6 Bq kg-1 within 2-3 days. The proposed solution may easily be implemented in radiochemical laboratories where this type of analysis is routinely done within environmental monitoring or other purposes.

Small conformational changes in IgG1 detected as acidic charge variants by cation exchange chromatography.

Fully characterizing the post-translational modifications present in charge variants of therapeutic monoclonal antibodies (mAbs), particularly acidic variants, is challenging and remains an open area of investigation. In this study, to test the possibility that chromatographically separated acidic fractions of therapeutic mAbs contain conformational variants, we undertook a mAb refolding approach using as a case study an IgG1 that contains many unidentified acidic peaks with few post-translational modifications, and examined whether different acidic peak fractions could be generated corresponding to these variants. The IgG1 drug substance was denatured by guanidine hydrochloride, without a reducing agent present, and gradually refolded by stepwise dialysis against arginine hydrochloride used as an aggregation suppressor. Each acidic chromatographic peak originally contained in the IgG1 drug substance was markedly increased by this stepwise refolding process, indicating that these acidic variants are conformational variants. However, no conformational changes were detected by small-angle X-ray scattering experiments for the whole IgG1, indicating that the conformational changes are minor. Chromatographic, thermal and fluorescence analyses suggested that the conformational changes are a localized denaturation effect centred around the aromatic amino acid regions. This study provides new insights into the characterization of acidic variants that are currently not fully understood.

Parts per billion of nitrite in microcrystalline cellulose by ion chromatography mass spectrometry with isotope labeled internal standard.

Regulatory authorities like the U.S. Food and Drug Administration (FDA) have set strict specification levels for N-nitrosamines in finished drug products. Nitrite is a potential precursor for the formation of probable carcinogenic N-nitrosamines when secondary or tertiary amines are also present in the active pharmaceutical ingredient (API) synthesis or drug formulation process. An accurate and sensitive determination of nitrite will be useful when a drug product manufacturer chooses to investigate the reaction kinetics between nitrite and amines or to select appropriate excipients for its drug formulation. Pharmaceutical excipient manufacturers may also need an accurate nitrite measurement to investigate the nitrite content in their excipients. This study details the development and validation of an ion chromatography mass spectrometry (IC-MS) method for trace nitrite determination in microcrystalline cellulose materials, one of the important pharmaceutical excipients used in many drug formulations. MS operated under selected ion monitoring mode was used to solve the commonly encountered interference issue with conductivity detection, and nitrite isotope internal standard was employed to address the ion suppression issue with MS detection. The installation of an after-column "jumper" to flush water with an auxiliary pump through the MS when it is not used for data collection avoided sensitivity loss due to trace salt accumulation in the ion source. Validation of the optimized method was satisfactory, with linearity of nitrite in the concentration range of 0.02-7.50 ppm (µg/g) having a regression coefficient of > 0.999, precision of RSD < 9.5% at 0.03 ppm and RSD < 3.4% at 0.4 ppm and recovery of 92.0-103.0%. The limit of detection and limit of quantitation were 0.005 and 0.016 ppm, respectively.

QuEChERS-assisted ion pair chromatography/fluorescence detection method for determination of antimigraine combination therapy in rabbit plasma samples: Application to a pharmacokinetic study.

Antimigraine combination therapy has shown significant effectiveness in relieving pain, as well as reducing the frequency, duration, and severity of migraine attacks if compared to a single migraine medication. This work represents the first analytical investigation for emphasizing the synergistic effect of combining ophthalmic beta blockers with triptans in migraine treatment. The presented study was conducted to investigate the pharmacokinetic profile of almotriptan (ALM), a serotonin (5-HT1B/1D) receptor agonist used to treat migraine, when coadministered with timolol (TIM) or verapamil (VER) which are considered as an adjuvant therapy in migraine prevention. Ion pair chromatography (IPC) with online fluorescence detection was applied to simultaneously detect and quantify the binary mixtures of ALM/TIM and ALM/VER in rabbit plasma samples. The separation was achieved using a Platinum C18 analytical column with a mobile phase composed of methanol: 35 mmol L-1 phosphate buffer solution containing 10 mmol L-1 SDS at pH = 6.8 (60:40 v/v). Several parameters were evaluated during the optimization of separation conditions including mobile phase composition, buffer concentration, buffer pH and concentration of ion pair reagent. A thorough investigation of the retention mechanism was performed, and the results showed that Coulomb forces were the main contributors to the overall retention mechanism, which may be hydrophobically assisted. QuEChERS extraction technique was utilized to extract the investigated drugs from plasma samples and a detailed study was carried out to optimize partition/extraction solvents, pH, extraction salts, sample volume and clean-up step. The method had a limit of detection and quantitation of 5.6 and 16.9 ng mL-1 for ALM in ALM/TIM mixture and 2.5 and 7.6 ng mL-1 for ALM in ALM/VER mixture, with an overall recovery not less than 95.22%. This newly proposed method offers a faster alternative to existing chromatographic methods for extraction and determination of ALM in binary mixtures with TIM or VER in rabbit plasma and provides a platform for studying pharmacokinetic parameters. The coadministration of either TIM or VER with ALM resulted in a notable rise in Cmax (maximum plasma concentration) and AUC (area under the plasma concentration-time curve) of ALM, implying possible alterations in the absorption and overall exposure of ALM.

Elucidation of composition of chlorine compounds in acidic sodium chlorite solution using ion chromatography.

With the spread of coronavirus infections, the demand for disinfectants, such as a sodium chlorite solution, has increased worldwide. Sodium chlorite solution is a food additive and is used in a wide range of applications. There is evidence that chlorous acid or sodium chlorite is effective against various bacteria, but the actual mechanism is not well understood. One reason for this is that the composition of chlorine-based compounds contained in sodium chlorite solutions has not been clearly elucidated. The composition can vary greatly with pH. In addition, the conventional iodometric titration method, the N,N-diethyl-p-phenylenediamine sulfate (DPD) method and the absorption photometric method cannot clarify the composition. In this study, we attempted to elucidate the composition of a sodium chlorite solution using absorption spectrophotometry and ion chromatography (IC). IC is excellent for qualitative and quantitative analysis of trace ions. Through this, we aimed to develop an evaluation method that allows anyone to easily determine the bactericidal power of sodium chlorite. We found that commercially available sodium chlorite solution is 80% pure, with the remaining 20% potentially containing sodium hypochlorite solution. In addition, when sodium chlorite solution became acidified, its absorption spectrum exhibited a peak at 365 nm. Sodium chlorite solution is normally alkaline, and it cannot be measured by the DPD method, which is only applicable under acidic conditions. The presence of a peak at 365 nm indicates that the acidic sodium chlorite solution contains species with oxidizing power. On the other hand, the IC analysis showed a gradual decrease in chlorite ions in the acidic sodium chlorite solution. These results indicate that chlorite ions may not react with this DPD reagent, and other oxidizing species may be present in the acidic sodium chlorite solution. In summary, when a sodium chlorite solution becomes acidic, chlorine-based oxidizing species produce an absorption peak at 365 nm. Sodium hypochlorite and sodium chlorite solutions have completely different IC peak profiles. Although there are still many problems to be solved, we believe that the use of IC will facilitate the elucidation of the composition of sodium chlorite solution and its sterilization mechanism.

Highly efficient separation of Am(III) and Pu(IV) from lean feeds and soil using an extraction chromatographic resin containing a diglycolamide in an ionic liquid.

A TODGA based extraction chromatographic resin containing an ionic liquid was used for the separation of actinide ions such as Am3+ and Pu4+ from samples such as lean effluents emanating from laboratory waste, environmental water as well as soil samples adjacent to a nuclear plant site. The methodology involved feed adjustment to 3 M HNO3 followed by conditioning of the column, loading, washing (3 M HNO3), and elution of the actinide ions. The elution of Am3+ was done using EDTA in a buffered medium (1 M guanidine carbonate) while that of Pu4+ was carried out using a mixture of 0.5 M oxalic acid and 0.5 M HNO3. The elution peaks were sharp with almost no tailing suggesting the efficiency of the separation method. The results obtained were compared with the literature results which suggested the high efficiency of the present method.

Model-assisted process development, characterization and design of continuous chromatography for antibody separation.

Continuous manufacturing in monoclonal antibody production has generated increased interest due to its consistent quality, high productivity, high equipment utilization, and low cost. One of the major challenges in realizing continuous biological manufacturing lies in implementing continuous chromatography. Given the complex operation mode and various operation parameters, it is challenging to develop a continuous process. Due to the process parameters being mainly determined by the breakthrough curves and elution behaviors, chromatographic modeling has gradually been used to assist in process development and characterization. Model-assisted approaches could realize multi-parameter interaction investigation and multi-objective optimization by integrating continuous process models. These approaches could reduce time and resource consumption while achieving a comprehensive and systematic understanding of the process. This paper reviews the application of modeling tools in continuous chromatography process development, characterization and design. Model-assisted process development approaches for continuous capture and polishing steps are introduced and summarized. The challenges and potential of model-assisted process characterization are discussed, emphasizing the need for further research on the design space determination strategy and parameter robustness analysis method. Additionally, some model applications for process design were highlighted to promote the establishment of the process optimization and process simulation platform.

Messenger RNA chromatographic purification: advances and challenges.

Messenger RNA (mRNA) technologies have shown great potential in prophylactic vaccines and therapeutic medicines due to their adaptability, rapidity, efficacy, and safety. The purity of mRNA determines the efficacy and safety of mRNA drugs. Though chromatographic technologies are currently employed in mRNA purification, they are facing challenges, mainly arising from the large size, relatively simple chemical composition, instability, and high resemblance of by-products to the target mRNA. In this review, we will first make a comprehensive analysis of physiochemical properties differences between mRNA and proteins, then the major challenges facing in mRNA purification and general considerations are highlighted. A detailed summary of the state-of-arts in mRNA chromatographic purification will be provided, which are mainly classified into physicochemical property-based (size, charge, and hydrophobicity) and chemical structure-based (phosphate backbone, bases, cap structure, and poly A tail) technologies. Efforts in eliminating dsRNA byproducts via post in vitro transcript (IVT) purification and by manipulating the IVT process to reduce the generation of dsRNA are highlighted. Finally, a brief summary of the current status of chromatographic purification of the emerging circular mRNA (circRNA) is provided. We hope this review will provide some useful guidance for the Quality by Design (QbD) of mRNA downstream process development.

Tetraethylenepentamine-derived carbon dots and tetraethylenepentamine co-immobilized silica stationary phase for hydrophilic interaction chromatography.

In this work, tetraethylenepentamine (TEPA) was used as precursor and reaction medium to prepare tetraethylenepentamine-functionalized carbon dots (TEPACDs), the resultant mixture was subsequently silanized and then grafted on the surface of bare silica. The obtained tetraethylenepentamine-functionalized carbon dots and tetraethylenepentamine co-modified silica stationary phase (Sil-TEPA/CDs) was characterized by multiple ways, such as Fourier transformed infrared spectroscopy (FTIR), elemental analysis and transmission electron microscope, which revealed the successful preparation of the mixed stationary phase and higher density of functional groups on co-modified stationary phase than precursor single-modified stationary phase. The synergistic effect of TEPACDs and TEPA was proved by comparing the separation performance of Sil-TEPA/CDs and Sil-TEPA toward amino acids, nucleosides, and nucleobases, which distinctly enhanced the selectivity of Sil-TEPA/CDs. Thus, 12 nucleosides and nucleobases and 11 amino acids was nicely separated on Sil-TEPA/CDs. By study the influences of the changes of mobile phase composition, mobile phase buffer concentration and buffer pH on the retention behaviors of Sil-TEPA and Sil-TEPA/CDs, it was found that both hydrophilic partitioning and adsorption of analytes on Sil-TEPA/CDs were enhanced benefit from the co-existence of TEPA and TEPACDs, which provided the analytes better separation performance. By comparing the column quality of Sil-TEPA/CDs with four commercially available columns, Sil-TEPA/CDs exhibited the best peak asymmetry of 0.98, and second best column efficiency of 43895 m-1 using guanosine as analyte. The RSD (n = 9) of the retention times of five selected analytes on Sil-TEPA/CDs were within 0.30-0.61% during 40 h of continuously elution, which implied excellent stability of prepared packing material.

2022 White Paper on Recent Issues in Bioanalysis: ICH M10 BMV Guideline & Global Harmonization; Hybrid Assays; Oligonucleotides & ADC; Non-Liquid & Rare Matrices; Regulatory Inputs (Part 1A - Recommendations on Mass Spectrometry, Chromatography and Sample Preparation, Novel Technologies, Novel Modalities, and Novel Challenges, ICH M10 BMV Guideline & Global Harmonization Part 1B - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV, Biomarkers/CDx/BAV, Immunogenicity, Gene & Cell Therapy and Vaccine).

The 16th Workshop on Recent Issues in Bioanalysis (16th WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on the ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2022 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1A) covers the recommendations on Mass Spectrometry and ICH M10. Part 1B covers the Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine. Part 2 (LBA, Biomarkers/CDx and Cytometry) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 15 of Bioanalysis, issues 15 and 14 (2023), respectively.

Mixed-Mode Chromatography and Its Role in Monoclonal Antibody Purification.

As the biopharmaceutical industry matures and embraces process intensification methodologies allied to the emergence of newer personalized medicines, a key constant is the regulatory need to purify products that satisfy the criteria of safety, quality, and efficacy in each batch of released product destined for clinical use. Downstream processing operations and in particular chromatographic separations continue to play a key role in manufacturing strategies with the industry being well served by commercially available resins that provide different options to purify a particular target molecule of interest. In recent years, mixed-mode chromatography, a technique based on multimode interactions between ligands and proteins, had attracted much attention. This short review will discuss the concept and benefit of mixed-mode chromatography in purification strategies and specifically look at its application in the purification of IgG subtype monoclonal antibodies, a key product class in today's industry.

Chromatographic Purification of Viral Vectors for Gene Therapy Applications.

Chromatography has been a mainstay in the downstream processing and purification of biopharmaceutical medicines. Until now, this has largely involved the purification of protein products such as recombinant enzymes and monoclonal antibodies using large-scale column chromatography methods. The development of advanced therapeutic medicinal products (ATMP) is heralding in a new era of therapeutics for a range of indications. These new therapeutics use diverse substances ranging from live stem cell preparations to fragments of nucleic acid enclosed in a viral delivery system. With these new technologies come new challenges in their purification. In this chapter, the challenges faced in producing and purifying viral vectors capable of delivering life-altering gene therapy to the patient will be discussed. Current methods of chromatography capable of adaptation to meet these new challenges and advancements that may be needed to increase the purification capabilities for these new products will also be discussed.

Hydroxyapatite Chromatography (HAC).

Hydroxyapatite (HA) is a mixed-mode media that has been used extensively for the purification of proteins and DNA since the 1950s. Hydroxyapatite possesses a distinctive selectivity that may be applied in the purification of a wide range of biomolecules: immunoglobulins, alkaline proteins, acidic proteins, and DNA. The functional groups of HA can both attract and repel the carboxyl and amino groups on target molecules. This unique selectivity is due to the modalities that can be employed, which are not possible with traditional anion-exchange and cation-exchange chromatography. HA is a powerful chromatography step for reducing host cell-derived impurities and aggregated product, where a 2-4 log reduction in host cell proteins, aggregates, endotoxin, and viruses are routinely achieved. This chapter describes the procedures for: efficiently packing and evaluating a HA column, purifying IgG and acidic proteins respectively using HA chromatography.

Single-Step Non-Chromatographic Purification of Recombinant Mammalian Proteins Using a Split Intein ELP Tag System.

Glycoprotein therapeutics are currently used by large patient populations and generate significant revenue for the biopharmaceutical industry. These therapeutic proteins are currently purified at industrial scale using individualized processes involving multiple chromatographic steps. In the absence of a viable affinity platform method, the required chromatographic steps are difficult to develop and inevitably lead to significant yield losses. Further, during preclinical development, there is a need for reliable platform technologies capable of performing high-throughput screening for biologic candidates. Although affinity tags can provide a solution to some of these challenges, they require specific affinity resins, and the tag itself can interfere with the target protein characteristics. Fusion protein systems consisting of elastin-like polypeptide (ELP) and self-cleaving split inteins such as Npu DnaE can serve as potential non-chromatographic platform technologies for the single-step purification of tagless glycoproteins expressed in mammalian cells. In this chapter, we demonstrate the use of this technology to obtain highly purified anti-ErbB2 ML39 single-chain variable fragment (scFv) expressed from Expi293F suspension cells.

Deciphering the human urine matrix: a new approach to simultaneously quantify the main ions and organic compounds by ion chromatography/mass spectrometry (IC-MS).

Analyzing the composition of (human) urine plays a major role in the fields of biology and medicine. Organic molecules (such as urea, creatine) and ions (such as chloride, sulfate) are the major compounds present in urine, the quantification of which allows for the diagnosis of a subject's health condition. Various analytical methods have been reported for studying urine components and validated on the basis of known and referenced compounds. The present work introduces a new method able to simultaneously determine both major organic molecules and ions contained in urine, by combining ion chromatography using a conductimetric detector with mass spectroscopy. The analysis of organic and ionized compounds (anionic and cationic) was achieved in double injections. For quantification, the standard addition method was used. Human urine samples were pre-treated (diluted and filtered) for IC-CD/MS analysis. The analytes were separated in 35 min. Calibration ranges (0-20 mg.L-1) and correlation coefficients (> 99.3%) as well as detection (LODs < 0.75 mg.L-1) and quantification (LOQs < 2.59 mg.L-1) limits were obtained for the main organic molecules (lactic, hippuric, citric, uric, oxalic acids, urea, creatine, and creatinine) and ions (chloride, sulfate, phosphate, sodium, ammonium, potassium, calcium, and magnesium) contained in urine. The intra- and inter-day accuracies of the analytes consistently ranged from 0.1 to 5.0%, and the precision was within 4.0%. For all analytes, no significant matrix effects were observed, and recoveries ranged from 94.9 to 102.6%. Finally, quantitative results of analytes were obtained from 10 different human urine samples.

Application of cellulose to chromatographic media: Cellulose dissolution, and media fabrication and derivatization.

As the cornerstone of chromatographic technology, the development of high-performance chromatographic media is a crucial means to enhance the purification efficiency of biological macromolecules. Cellulose is a popular biological separation medium due to its abundant hydroxyl group on the surface, easy modification and, weak non-specific adsorption. In this paper, the development of cellulosic solvent systems, typical preparation methods of cellulosic chromatographic media, and the enhancement of chromatographic properties of cellulosic chromatographic media by polymeric ligand grafting strategies and their mechanism of action are reviewed. Ultimately, based on the current research status, a promising outlook for the preparation of high-performance cellulose-based chromatographic media was presented.

Aptamer-Based Chromatographic Methods for Efficient and Economical Separation of Leukocyte Populations.

The manufacturing process of chimeric antigen receptor T cell therapies includes isolation systems that provide pure T cells. Current magnetic-activated cell sorting and immunoaffinity chromatography methods produce desired cells with high purity and yield but require expensive equipment and reagents and involve time-consuming incubation steps. Here, we demonstrate that aptamers can be employed in a continuous-flow resin platform for both depletion of monocytes and selection of CD8+ T cells from peripheral blood mononuclear cells at low cost with high purity and throughput. Aptamer-mediated cell selection could potentially enable fully synthetic, traceless isolations of leukocyte subsets from a single isolation system.

Capillary electrokinetic chromatography for studying interactions between ß-blockers and Intralipid emulsion.

Toxicity of ß-blockers is one of the most common causes of poison-induced cardiogenic shock throughout the world. Therefore, methodologies for in vivo removal of the drugs from the body have been under investigation. Intralipid emulsion (ILE) is a common commercial lipid emulsion used for parenteral nutrition, but it has also been administered to patients suffering from drug toxicities. In this work, a set of ß-blockers of different hydrophobicity's (log KD values ranging from 0.16 to 3.8) were investigated. The relative strength of the interactions between these compounds and the ILE was quantitatively assessed by means of binding constants and adsorption constants of the formed ß-blocker-ILE complexes. The binding constants were determined by capillary electrokinetic chromatography and the adsorption constants were calculated based on different adsorption isotherms. Expectedly, the binding constants were strongly related to the log KD values of the ß-blockers. The binding and adsorption constants also show that less hydrophobic ß-blockers interact with ILE, suggesting that this emulsion could be useful for capturing such compounds in cases of their overdoses. Thus, the use of ILE for treatment of toxicities caused by a larger range of ß-blockers is worth further investigation.

Applications of ion chromatography in urine analysis: A review.

Ion chromatography (IC) plays a crucial role in urine analysis for diverse medical diagnoses. This paper reviews a comprehensive investigation into urine pretreatment techniques, as well as the design and development of IC systems for the measurement of various chemicals. Prior to analysis, urine samples commonly undergo pretreatment procedures such as dilution, filtration, purification, and concentration. These steps effectively eliminate interfering factors and facilitate the accurate and sensitive analysis of ultra-trace components. To separate and quantify different chemical elements or ions present in urine, a range of homemade or commercially available columns coupled with various detectors were employed. This study focuses on the analysis of chemicals such as heavy metals, halogens, pesticides, drugs, and other essential or toxic substances by IC methods.