Production of Biomass-Derived p-Hydroxybenzamide: Synthesis of p-Aminophenol and Paracetamol.

As we work to transition the modern society that is based on non-renewable chemical feedstocks to a post-modern society built around renewable sources of energy, fuels, and chemicals, there is a need to identify the renewable resources and processes for converting them to platform chemicals. Herein, we explore a strategy for utilizing the p-hydroxybenzoate in biomass feedstocks (e. g., poplar and palm trees) and converting it into a portfolio of commodity chemicals. The targeted bio-derived product in the first processing stage is p-hydroxybenzamide produced from p-hydroxybenzoate esters found in the plant. In the second stage a continuous reaction process converts the p-hydroxybenzamide to p-aminophenol via the Hofmann rearrangement and recovers the unreacted p-hydroxybenzamide. In the third stage the p-aminophenol can be acetylated to form paracetamol, which is readily isolated by liquid/liquid extraction at >95 % purity and an overall p-hydroxybenzamide-to-paracetamol process yield of ~90 %. We explore how utilization of protecting groups alters the challenges in this process and expands the portfolio of possible products to include p-(methoxymethoxy)aniline and N-acetyl-p-(methoxymethoxy)aniline. These target compounds could become value-added renewably-sourced platform chemicals that could be used to produce biodegradable plastics, pigments, and pharmaceuticals.

High-dose exposure to butylparaben impairs thyroid ultrastructure and function in rats.

Parabens (PBs) are a class of preservatives commonly used in cosmetics and pharmaceuticals. Studies have shown that these compounds may act as endocrine disruptors, affecting thyroxine levels in humans. PBs with longer chain substituents, such as butylparaben (BuP), are less prone to complete biotransformation and are therefore more likely to accumulate in the body. In this study, the effect of high-dose exposure to BuP on thyroid microstructure, ultrastructure, and function was investigated in rats. 50 mg/kg bw per day of BuP was injected subcutaneously into the neck of rats for 4 weeks. Rat thyroid weight, microstructure, and ultrastructure were determined, and the levels of thyroid sodium/iodide symporter (NIS), serum thyroid hormones, and thyroid autoantibodies were measured. The human thyroid cell line was used to study the mechanism of BuP on thyroid epithelial cells. The weight of the thyroid gland of BuP-exposed rats was increased, the structure of the thyroid follicles was irregular and damaged, the mitochondria and rough endoplasmic reticulum were swollen and damaged, and the microvilli at the tip of the epithelium were reduced and disappeared. Serum total T3, total T4, free T3, and free T4 were decreased in BuP-exposed rats, and TSH, peroxidase antibody, and thyroglobulin antibody were increased. In vitro, BuP decreased the level of NIS in thyroid epithelial cells, inhibited proliferation and viability, and induced apoptosis in a dose-dependent manner. This study demonstrated that high-dose exposure to BuP induced structural, ultrastructural, and functional impairment to the thyroid gland of rats, which may be one of the factors leading to hypothyroidism.

Grouping of esters of 4-hydroxybenzoic acid for hazard assessment.

Hazardous properties of a large number of esters of 4-hydroxybenzoic acid (parabens) have been proposed by ECHA to be assessed as a group. We recommend to restrict the grouping approach to short chain esters, i.e. methyl, ethyl, propyl and butyl paraben which are very similar in chemical structures, physicochemical properties, toxicokinetics, and hazardous properties. While these parabens show a weak estrogenicity in some in vitro or in vivo screening assays, they do not induce estrogen-receptor-mediated adverse effects in intact animals. Therefore, there is no support regarding classification and labeling of endocrine disruption or reproductive toxicity of these parabens.

Urinary concentrations of bisphenol A, parabens and benzophenone-type ultra violet light filters in relation to sperm DNA fragmentation in young men: A chemical mixtures approach.

People are daily exposed to multiple endocrine disruptor compounds (EDCs) that may interfere with different molecular and cellular processes, promoting a potential estrogenic, androgenic, or anti-androgenic state. However, most epidemiological studies attempting to establish relationships between EDCs exposure and health effects are still considering individual compounds. A few studies have shown associations between exposure to individual non-persistent EDCs and sperm DNA fragmentation (SDF) in different male populations. Thus, the aim of this study was to investigate associations between combined exposure to non-persistent EDCs and SDF index in young men. A cross-sectional study was conducted with 158 healthy university students from Southeaster Spain. The participants provided spot urine and semen samples on the same day. The concentrations of urinary bisphenol A (BPA), benzophenones [2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), 4-hydroxybenzophenone (4OHBP)], and parabens (methylparaben, ethylparaben, propylparaben, butylparaben) were measured by dispersive liquid-liquid microextraction and ultrahigh-performance liquid chromatography with tandem mass spectrometry detection. SDF was analysed using a Sperm Chromatin Dispersion test. Statistical analyses were carried out using Bayesian Kernel Machine Regression models to evaluate associations between combined exposure to these compounds and SDF index while adjusting by relevant covariates. The increase in urinary concentration of 4OHBP was found to be the most important contributor to the negative association between urinary EDCs concentrations and SDF index, being of -5.5 % [95 % CI: -10.7, -0.3] for those in percentile 50, and - 5.4 % [95 % CI: -10.8, -0.1] for those in percentile 75. No significant associations were observed between other EDCs and SDF index. Our findings show that urinary 4OHBP levels may be associated with a decrease in the SDF index. Nonetheless, the effects we observed were likely to be small and of uncertain clinical significance. Further research is needed to replicate our findings in other male populations.

Occurrence, distribution, and risk assessment of parabens in the surface water of Terengganu River, Malaysia.

The concentration, distribution, and risk assessment of parabens were determined in the surface water of the Terengganu River, Malaysia. Target chemicals were extracted via solid-phase extraction, followed by high-performance liquid chromatography analysis. Method optimization produced a high percentage recovery for methylparaben (MeP, 84.69 %), ethylparaben (EtP, 76.60 %), and propylparaben (PrP, 76.33 %). Results showed that higher concentrations were observed for MeP (3.60 µg/L) as compared with EtP (1.21 µg/L) and PrP (1.00 µg/L). Parabens are ubiquitously present in all sampling stations, with >99 % of detection. Salinity and conductivity were the major factors influencing the level of parabens in the surface water. Overall, we found no potential risk of parabens in the Terengganu River ecosystem due to low calculated risk assessment values (risk quotient < 1). In conclusion, parabens are present in the river, but their levels are too low to pose risks to aquatic organisms.

Disparate toxicity mechanisms of parabens with different alkyl chain length in freshwater biofilms: Ecological hazards associated with antibiotic resistome.

As emerging organic pollutants, parabens are of global concern because of their ubiquitous presence and adverse effects. However, few researchers have addressed the relationship between parabens' structural features and toxicity mechanisms. This study conducted theoretical calculations and laboratory exposure experiments to uncover the toxic effects and mechanisms of parabens with different alkyl chains in freshwater biofilms. The result demonstrated that parabens' hydrophobicity and lethality increased with their alkyl-chain length, whereas the possibility of chemical reactions and reactive sites were unchanged despite the alkyl-chain length alteration. Due to the hydrophobicity variation, parabens with different alkyl-chain presented different distribution patterns in cells of freshwater biofilms and consequently induced distinct toxic effects and led to diverse cell death modes. The butylparaben with longer alkyl-chain preferred to stay in the membrane and altered membrane permeability by non-covalent interaction with phospholipid, which caused cell necrosis. The methylparaben with shorter alkyl-chain preferred to enter into the cytoplasm and influence mazE gene expression by chemically reacting with biomacromolecules, thereby triggering apoptosis. The different cell death patterns induced by parabens contributed to different ecological hazards associated with antibiotic resistome. Compared with butylparaben, methylparaben was more likely to spread ARGs among microbial communities despite its lower lethality.

Parabens Permeation through Biological Membranes: A Comparative Study Using Franz Cell Diffusion System and Biomimetic Liquid Chromatography.

Parabens (PBs) are used as preservatives to extend the shelf life of various foodstuffs, and pharmaceutical and cosmetic preparations. In this work, the membrane barrier passage potential of a subset of seven parabens, i.e., methyl-, ethyl-, propyl- isopropyl, butyl, isobutyl, and benzyl paraben, along with their parent compound, p-hydroxy benzoic acid, were studied. Thus, the Franz cell diffusion (FDC) method, biomimetic liquid chromatography (BLC), and in silico prediction were performed to evaluate the soundness of both describing their permeation through the skin. While BLC allowed the achievement of a full scale of affinity for membrane phospholipids of the PBs under research, the permeation of parabens through Franz diffusion cells having a carbon chain > ethyl could not be measured in a fully aqueous medium, i.e., permeation enhancer-free conditions. Our results support that BLC and in silico prediction alone can occasionally be misleading in the permeability potential assessment of these preservatives, emphasizing the need for a multi-technique and integrated experimental approach.

Read-across and new approach methodologies applied in a 10-step framework for cosmetics safety assessment - A case study with parabens.

Parabens are esters of para-hydroxybenzoic acid that have been used as preservatives in many types of products for decades including agrochemicals, pharmaceuticals, food and cosmetics. This illustrative case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework in practice. It aims at establishing a proof-of-concept for the value added by new approach methodologies (NAMs) in read-across (RAX) for use in a next-generation risk assessment (NGRA) in order to assess consumer safety after exposure to PP-containing cosmetics. In addition to structural and physico-chemical properties, in silico information, toxicogenomics, in vitro toxicodynamic, toxicokinetic data from PBK models, and bioactivity data are used to provide evidence of the chemical and biological similarity of PP and analogues and to establish potency trends for observed effects in vitro. The chemical category under consideration is short (C1-C4) linear chain n-alkyl parabens: methylparaben, ethylparaben, propylparaben and butylparaben. The goal of this case study is to illustrate how a practical framework for RAX can be used to fill a hypothetical data gap for reproductive toxicity of the target chemical PP.

Identifying potential paraben transformation products and evaluating changes in toxicity as a result of transformation.

Parabens are a class of compounds often used as preservatives in personal care products, pharmaceuticals, and food. They have received attention recently due to findings that demonstrate estrogenic impacts and other adverse effects of parabens. Release into wastewater effluent is considered a major contributor to the spread of parabens into surface water. Current regulations in areas such as Japan, Europe, and Southeast Asia limit the concentrations of parabens that can be used in formulations but do not address concentrations discharged into waterbodies. Recent studies suggest that parent parabens are effectively eliminated by transformation during the wastewater treatment processes. Common tertiary treatments include ultrafiltration, chlorination, UV disinfection and ozonation. Ultrafiltration is used to remove solids before a disinfection step. Of the disinfection steps, ozonation is often the most effective at removing parabens. Not much is known about the toxicities of paraben transformation products. Of the transformation products, chlorinated parabens and PHBA are the most studied. Previous studies have shown that chlorinated parabens have greatly reduced estrogen agonistic activity when compared with the activity of parents. However, more recent studies have found that halogenated parabens actually have estrogen antagonistic activity. Further research involving chlorinated parabens could include other toxic endpoints. No known studies have evaluated adverse effects of oxygenated parabens. Parabens can interact with chlorine residues in the environment and form chlorinated products, this will occur at a faster rate during chlorination. Ozonation will oxidize parabens and UV disinfection can both oxidize and halogenate parabens. All studies determining potential transformation products have been done in laboratory settings or specific conditions. Further research is needed to determine if these transformations occur in situ. PRACTITIONER POINTS: Common chemical processes utilized by wastewater treatment facilities are effective at transforming parabens. Paraben transformation products are released in greater concentration in effluent than parent paraben compounds. Halogenated transformation products have been identified as estrogen receptor antagonists.

A survey of parabens in aquatic environments in Hanoi, Vietnam and its implications for human exposure and ecological risk.

Seven parabens including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), iso-propylparaben (iPrP), butylparaben (BuP), benzylparaben (BzP), and heptylparaben (HepP) were determined in bottled water, tap water, river water, lake water, and wastewater samples collected from Hanoi, Vietnam, using solid phase extraction (SPE) followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The highest total concentration of parabens were measured in wastewater (range, 27.3-1050 ng/L; mean/median, 268/175 ng/L), followed by lake water (range, 18.0-254 ng/L; mean/median, 51.7/58.5 ng/L), river water (range, 16.5-52.1 ng/L; mean/median, 32.1/42.6 ng/L), tap water (range, 5.01-54.3 ng/L; mean/median, 28.6/41.1 ng/L), and bottled water (range, 1.56-39.9 ng/L; mean/median, 6.92/9.19 ng/L). Methylparaben and propylparaben were the predominant compounds found in all samples. The mean estimated human exposure dose of parabens through drinking bottled water was 0.27 ng/kg-bw/day, which is 6 orders of magnitude below the safety threshold recommended by the Joint FAO/WHO Expert Committee on Food Additive in 1974 (10 mg/kg-bw/day). Concentrations of parabens measured in river water, lake water, and wastewater samples were assessed to pose low to moderate ecological risks to aquatic organisms (0.1 < RQ < 1). Methyl, ethyl, and propyl parabens exhibited significant correlations in water samples.

ZrO2@chitosan composite for simultaneous photodegradation of three emerging contaminants and antibacterial application.

Emerging contaminants (ECs) are often detected in water bodies due to their prevalent use combined with inefficiency of the conventional wastewater treatment plants for their complete removal. Elimination of ECs using photocatalysis as a tertiary treatment can be a sustainable option for the reuse wastewater. Reported herewith is a photocatalyst, chitosan-based zirconia hybrid composite (ZrO2CTS-HC) for the individual/ simultaneous degradation of multiple ECs like Congo red (CR), Methyl orange (MO) and 4-hydroxybenzoic acid (4-HA) under visible light irradiation. Successfully synthesized ZrO2CTS-HC as confirmed by theoretical and various characterization techniques depicted photodegradation efficiency of 91.11, 69.11 and 78.40% for CR, MO and 4-HA respectively (SD 0.5-0.95; HPLC) aided by the reactive hydroxyl radical. Probable degradation mechanism supported by LC-MS/MS, COD and TOC along with reusability and antibacterial ability towards E.Coli & S.aureus is also reported. ZrO2CTS-HC can be a good option for elimination of residual ECs during tertiary treatment.

Review of aluminum, paraben, and sulfate product disclaimers on personal care products.

BACKGROUND: Product disclaimers listed on personal care products face limited regulation. These disclaimers may be helpful or may mislead the public. OBJECTIVE: Review the evidence supporting the potential harms of 3 compounds commonly addressed by product disclaimers: parabens, aluminum, and sulfates. METHODS: Reported cases of adverse events to these compounds were identified. Trends in allergic contact dermatitis reactions to chemicals used in place of these compounds were also identified. RESULTS: There is limited evidence that parabens and aluminum pose a threat to human health; there is even less evidence that topical sulfate-containing products pose a danger to consumers. In the setting of paraben avoidance, there has been a steady increase in cases of allergic contact dermatitis to preservatives that are more allergenic, specifically the isothiazolinones. LIMITATIONS: Assessment of the toxicology of these compounds is ongoing and may change with new data. CONCLUSION: There is limited evidence that parabens, aluminum, and sulfates used in personal care products pose a health risk. There is evidence that avoidance of parabens has resulted in an epidemic of allergic contact dermatitis to isothiazolonine preservatives.

Strategies to improve the challenges of classic dispersive liquid-liquid microextraction for determination of the parabens in personal care products-One step closer to green analytical chemistry.

Gas flow-assisted dispersive liquid-phase microextraction based on deep eutectic solvent was used to determine parabens in personal care products such as mouthwash, lidocaine gel, aloe vera gel, and skin tonic. A homemade extraction device was innovated, in which by passing the stream of gas bubbles through the deep eutectic solvent a thin layer of the extraction phase is coated on the surface of the bubbles. The extraction is finally achieved when the bubbles are going up through the sample. The single-factor experiments and response surface methodology were applied to optimize the independent variables. The linear range of the method was 0.5 to 1000 µg L-1, the coefficient of determination for the goal analytes was higher than 0.9989, the instrumental limit of detections were in the range 0.2-0.3 µg L-1, and the instrumental limit of quantifications were in the range 0.5-1.1 µg L-1, the relative standard deviations were <5.2% for repeatability and <11.2% for intermediate precision, and the enrichment factors were 66 to 87 obtained under the optimized conditions. A spiking approach by means of standard material was used to estimate accuracy. The relative recoveries were in the range 95.8-105.2%. By using mentioned strategies, the organic waste and energy consumption reduced, toxic reagents replaced with safer ones, and operator safety enhanced. Accordingly, these benefits have been simultaneously attained and, the proposed method was one step closer to automation and sustainable analytical chemistry.

Environmental obesogens (bisphenols, phthalates and parabens) and their impacts on adipogenic transcription factors in the absence of dexamethasone in 3T3-L1 cells.

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that are capable of blocking or mimicking the action of bioidentical hormones. Obesogenic EDCs, commonly called obesogens, play an important role in adipogenesis. This study was carried out to determine the effects of select obesogens and their alternatives on adipogenesis in 3T3-L1 cells under dexamethasone (DEX)-free conditions. Preadipocytes were treated with a cocktail of 3-isobutyl-1-methylxanthine (IBMX) and insulin to which an obesogen (viz., bisphenol A (BPA) or its analogs BPS and BPF; dioctyl terephthalate; tris (2-ethylhexyl) trimellitate; or various parabens) had been added. A mixture containing IBMX, insulin, and DEX, which constitute the typical hormonal cocktail required for adipocyte differentiation, was used as the control against which the other groups were measured. The obesogens and the PBA analogs all had evident adipogenic effects under DEX-free conditions, as was determined by estimating the lipid accumulation levels in the cells using Oil Red O staining. Furthermore, the expression of adipogenic transcription factors (CCAAT/enhancer-binding protein-alpha, peroxisome proliferator-activated receptor-gamma, and adipocyte protein 2) was induced by 20 µM of BPA, BPS, or BPF at both the mRNA and protein levels, as determined through reverse transcription-polymerase chain reaction and western blot assays. Taken together, the results reveal that adipocyte differentiation can be induced by obesogens and their alternatives in the absence of DEX.

Phenolic Profiles of Ten Australian Faba Bean Varieties.

Although Australia is the largest exporter of faba bean globally, there is limited information available on the levels of bioactive compounds found in current commercial faba bean varieties grown in this country. This study profiled the phenolic acid and flavonoid composition of 10 Australian faba bean varieties, grown at two different locations. Phenolic profiling by HPLC-DAD revealed the most abundant flavonoid to be catechin, followed by rutin. For the phenolic acids, syringic acid was found in high concentrations (72.4-122.5 mg/kg), while protocatechuic, vanillic, p-hydroxybenzoic, chlorogenic, p-coumaric, and trans-ferulic acid were all found in low concentrations. The content of most individual phenolics varied significantly with the variety, while some effect of the growing location was also observed. This information could be used by food processors and plant breeders to maximise the potential health benefits of Australian-grown faba bean.

Design of Multifaceted Antioxidants: Shifting towards Anti-Inflammatory and Antihyperlipidemic Activity.

Oxidative stress and inflammation are two conditions that coexist in many multifactorial diseases such as atherosclerosis and neurodegeneration. Thus, the design of multifunctional compounds that can concurrently tackle two or more therapeutic targets is an appealing approach. In this study, the basic NSAID structure was fused with the antioxidant moieties 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHB), its reduced alcohol 3,5-di-tert-butyl- 4-hydroxybenzyl alcohol (BHBA), or 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), a hydrophilic analogue of α-tocopherol. Machine learning algorithms were utilized to validate the potential dual effect (anti-inflammatory and antioxidant) of the designed analogues. Derivatives 1-17 were synthesized by known esterification methods, with good to excellent yields, and were pharmacologically evaluated both in vitro and in vivo for their antioxidant and anti-inflammatory activity, whereas selected compounds were also tested in an in vivo hyperlipidemia protocol. Furthermore, the activity/binding affinity of the new compounds for lipoxygenase-3 (LOX-3) was studied not only in vitro but also via molecular docking simulations. Experimental results demonstrated that the antioxidant and anti-inflammatory activities of the new fused molecules were increased compared to the parent molecules, while molecular docking simulations validated the improved activity and revealed the binding mode of the most potent inhibitors. The purpose of their design was justified by providing a potentially safer and more efficient therapeutic approach for multifactorial diseases.

Determination of six parabens in biological samples by magnetic solid-phase extraction with magnetic mesoporous carbon adsorbent and UHPLC-MS/MS.

Although parabens are useful due to their antiseptic properties, their widespread use has caused concerns regarding their potential toxicological effects. In this study, a novel magnetic solid-phase extraction combined with ultra-high-performance liquid chromatography-tandem mass spectrometry (MSPE-UHPLC-MS/MS) was developed, based on ordered magnetic mesoporous carbon (MMC), for paraben analysis. The MMC was prepared by soft-template synthesis, with a unique pore structure and a highly specific surface response, indicating potential as an excellent adsorbent. Several parameters affecting the paraben extraction efficiency were investigated and a novel method for paraben analysis in serum and urine samples using MSPE-UHPLCMS/MS was developed. The concentrations of methylparaben, ethylparaben, isopropylparaben, and propylparaben in these samples were 0.0380-4.36, 0.460-9.65, 0.0118-0.770, and 0.0363-0.641 µg/L, respectively, whereas isobutylparaben and butylparaben were not detected. Furthermore, satisfactory recoveries of 76.4-121% with relative standard deviations (n = 5) of 1.9-8.6% were obtained. Therefore, the developed MSPE-UHPLC-MS/MS method was efficient, highly sensitive, and reliable for analysing parabens in complex biological samples.

Nipagin-Functionalized Porphyrazine and Phthalocyanine-Synthesis, Physicochemical Characterization and Toxicity Study after Deposition on Titanium Dioxide Nanoparticles P25.

Aza-porphyrinoids exhibit distinct spectral properties in UV-Vis, and they are studied in applications such as photosensitizers in medicine and catalysts in technology. The use of appropriate peripheral substituents allows the modulation of their physicochemical properties. Phthalocyanine and sulfanyl porphyrazine octa-substituted with 4-(butoxycarbonyl)phenyloxy moieties were synthesized and characterized using UV-Vis and NMR spectroscopy, as well as mass spectrometry. A comparison of porphyrazine with phthalocyanine aza-porphyrinoids revealed that phthalocyanine macrocycle exhibits higher singlet oxygen generation quantum yields, reaching the value of 0.29 in DMF. After both macrocycles had been deposited on titanium dioxide nanoparticles P25, the cytotoxicities and photocytotoxicities of the prepared materials were studied using a Microtox® acute toxicity test. The highest cytotoxicity occurred after irradiation with a red light for the material composed of phthalocyanine deposited on titania nanoparticles.

Promising anticancer activity of polysaccharides and other macromolecules derived from oyster mushroom (Pleurotus sp.): An updated review.

Cancer dominates among many causes of mortality worldwide. Traditional chemotherapeutic agents are powerful anti-cancer agents employed for treatment of this deadly disease. However, they are always associated with toxic side effects and immunosuppression making person more vulnerable to tumor relapse and fatalities. A promising alternative could be identification, isolation and transfer of naturally occurring bioactive macromolecules to the tumorigenic population. Oyster mushroom, a major source of nutraceuticals, belonging to class basidiomycetes of kingdom Mycota is known to have immense therapeutic properties. It is a reservoir of macromolecules like ß-glucan, α-glucan, resveratrol, concanavalin A, cibacron blue affinity protein, p-hydroxybenzoic acid, ergosterol, linoleic acid etc. that are responsible for mediating anti-tumor, immunomodulatory, antioxidant, and anti-diabetic roles. Various studies have shown that extracts derived from oyster mushroom is rich in polysaccharides like ß-glucan and other macro molecules which have an anti-proliferative effect against cancer cell lines, without harming the normal cells. This review presents a brief highlight of the work covering the overall significance of oyster mushroom in different types of cancer treatment. It also explores the immunomodulatory effects of polysaccharides, proteoglycans and polypeptides derived from oyster mushroom that boosts the immune system to overcome the limitation of traditional cancer therapies.

A simple and rapid HPLC method for determination of parabens and their degradation products in pharmaceutical dosage forms.

A stability-indicating HPLC method was developed for the simultaneous determination of paraben mixture and its degradation products in effervescent potassium chloride tablets. The chromatographic separation was achieved on a Waters Cortecs C18 column (2.7 µm, 4.6 × 150 mm) using gradient elution. The optimized mobile phase consisted of 0.1% orthophosphoric acid in purified water as solvent A and purified water, acetonitrile, and orthophosphoric acid (100:900:1, v/v) as solvent B. The flow rate was 0.8 mL/min, and column temperature was maintained at 35°C. The injection volume was 10 µL, and UV detection was carried out at 254 nm. The selectively developed method has optimal separation among p-hydroxybenzoic acid, methylparaben, ethylparaben, propylparaben, and butylparaben peaks in the presence of specified and unspecified degradation products in the determination of drug product. The mass balance obtained from forced degradation studies was ≥95% and thus proves the stability-indicating property of the developed method. The developed reversed-phase HPLC method has been validated according to the International Conference on Harmonization guidelines. The correlation coefficients for all the peaks were >0.9999. The results of the other validation parameters were found within the limits. Finally, the optimized method was used in the quality control lab for stability analysis.