Pharmacy and Drug Development

Abstract

Heavy metals, existing in diverse chemical states, present analytical challenges requiring preconcentration techniques before determination. The study aims to evaluate heavy metal contamination in water sources across Southern Nigeria, employing rigorous analytical and sampling methodologies. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) was used for the multi-element analysis, capitalizing on its broad linear range (4–6 orders of magnitude) and reduced matrix interference compared to atomic absorption spectroscopy (AAS). Sampling followed strict protocols: containers were pre-cleaned via acid-wash (nitrate/phosphorus) or detergent-rinse (conductivity, pH, metals), and water was collected from mid-current points across 13 sites in Edo, Cross River, Akwa-Ibom, and Delta States. Results revealed arsenic levels exceeding WHO guidelines in SP4 (Obaretin River, Edo; 0.103 mg/L), SP11 (Esuk Nsidung, Cross River; 0.165 mg/L), and SP13 (Okada River, Edo; 0.109 mg/L). Aluminum concentrations were elevated in SP4 (1.766 mg/L), SP8 (1.112 mg/L), and SP10 (1.351 mg/L). Other metals (Cd, Co, Cr, Cu, Pb, Zn) generally fell within acceptable limits. Iron was highest in SP6 (3.002 mg/L), while manganese remained below thresholds. The presence of arsenic above safety limits highlights pollution risks, potentially linked to anthropogenic activities or geological factors. These results underscore significant health risks from arsenic (carcinogenic, linked to IQ reduction) and lead (neurotoxic), emphasizing vulnerabilities in children due to higher exposure rates and developmental sensitivity. Regulatory failures exacerbate these risks, as evidenced by undocumented toxins in consumer goods and inadequate safety labeling. The study concludes that while most sites are relatively safe, targeted interventions by regulatory and state agencies are crucial to safeguard drinking water, alongside stricter industrial regulations and public awareness campaigns.

Introduction

Heavy metals can exist in various states in natural water and food [1,2]. Analyzing heavy metals in natural water is challenging due to their existence in various chemical forms (e.g., mercury as organic complexes, arsenic in different oxidation states), which often necessitates converting them into measurable forms [3]. Direct determination frequently lacks sufficient sensitivity, and some analytical methods require solid samples or are sensitive to the metal's specific form. Consequently, preconcentration techniques like evaporation, solvent extraction, or sorption are typically essential steps before analysis [4,5]. While highly sensitive instrumental methods (like atomic absorption spectrometry, spectrophotometry, various chromatographic methods, and newer techniques for specific metals) are employed, preconcentration remains crucial in many cases due to low concentrations [6-11]. Solvent extraction using macrocyclic extractants offers a highly selective approach for separating certain metals [12-13]. Despite these complexities, the study suggests that natural water, with appropriate preconcentration and analytical methods, is comparatively straightforward to analyze for heavy metal content.

Trace analyses of metals, heavy metals, elemental analysis, chemical analysis, and isotopic analysis are provided by ICP/OES, ICP-MS, inductively coupled plasma (ICP), atomic absorption spectroscopy (AAS), and other methods [14-15]. ICP has been commercially available for over 40 years and is used to measure trace metals in a variety of solutions. ICP can be performed using various techniques [16], including Inductively coupled plasma-optical emission Spectroscopy (ICP-OES) and inductively coupled plasma-mass spectrometry (ICP-MS). Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) measures trace metals by converting a sample solution into an aerosol introduced into a superheated plasma. The plasma desolvates, vaporizes, dissociates, and excites the sample atoms, causing them to emit element-specific light wavelengths; the intensity of this emission corresponds to the element's concentration [17,18]. This technique is vital for detecting toxic heavy metals, which can contaminate products from sources like catalysts, raw materials, or equipment. Successful analysis requires meticulous sample preparation, typically involving dissolution in a compatible solvent like dilute acid to prevent interference or nebulizer clogging, and ensuring standards and blanks match the sample matrix. The nebulization step is a critical source of potential noise. Instrument calibration using standards within the method's wide linear range is essential, and appropriate wavelengths must be selected based on target concentration and potential spectral interference from other [19-21].

Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is the most sensitive technique for trace element analysis, achieving exceptionally low detection limits typically ranging from 0.01 to 1 µg/L (or µg/g) in solution [22,23]. It excels as a rapid multi-element method, capable of quantifying over 60 elements simultaneously in a single analysis, a significant advantage over techniques like Graphite Furnace Atomic Absorption (GFAA) that require individual element measurement. A key strength is its definitive identification capability based on multiple isotopes, making it inherently less susceptible to interferences. Sample preparation is typically straightforward, often involving simple dilution of the sample in 1% nitric acid [22,23].

Atomic Absorption Spectroscopy (AAS) quantifies chemical elements by measuring the absorption of specific wavelengths of light by free, ground-state atoms in a gaseous state [24]. Primarily used to determine the concentration of an analyte (over 70 elements possible) in solution or solids, it relies on the Beer-Lambert law, requiring standards of known concentration to correlate measured absorbance with analyte concentration. Flame AAS (FAAS), a common and reliable technique for metals/metalloids, involves aspirating a liquid sample into a high-temperature flame (e.g., acetylene/air). The flame converts the sample into free atoms via stages like desolvation, vaporization, and atomization, though ionization (reducing sensitivity) and other phase transfer interferences can occur [25]. Element-specific light, generated by a lamp with a cathode made of the analyte, passes through the flame. A detector measures the reduction in light intensity due to atomic absorption, which is directly related to the analyte's concentration, producing a steady-state signal during aspiration [25].

Employing rigorous analytical and sampling methodologies, this study aims to evaluate heavy metal contamination in Southern Nigerian water sources. ICP analysis is utilized because it can measure multiple elements simultaneously and exhibits a longer linear range (4-6 orders of magnitude) compared to AAS (2-3 orders). Furthermore, ICP experiences less chemical interference (due to the plasma's high temperature) and less matrix interference (due to its sample introduction method) than AAS.

Method

General Preparation and Sampling Considerations

Sampling container preparation

Containers and glassware reused between sampling runs must be thoroughly cleaned and rinsed before initial use and after each run. The appropriate cleaning method depends on the target analyte:

Method 1 General wash for conductivity, total solids, turbidity, pH, total alkalinity, heavy metals: Wearing latex gloves, scrub each item with phosphate-free detergent and a brush. Rinse three times with cold tap water, followed by three rinses with distilled or deionized water.

Method 2 Acid wash for nitrates and phosphorus: Wearing latex gloves, each item is scrubbed with phosphate-free detergent and a brush. Rinse three times with cold tap water. Then rinse once with 10% hydrochloric acid (HCl), followed by three rinses with deionized water.

Sample collection protocol

Samples are always collected from the stream's main current, avoiding stagnant water. The outside curve of bends where the main flow concentrates is targeted. In shallow areas, the central current for collection is waded through carefully. For deep sites, a boat positioned in the main current is used. These steps are followed when gathering water samples for field or laboratory analysis.

For Screw – Cap Bottles

Water samples must be collected using the following procedure to ensure integrity. Before sampling, clearly label the sample bottle with the site number, date, and time. Immediately before collection, remove the bottle cap, taking care to avoid any contact with the interior surface of the bottle or cap; hold the bottle securely near its base. Submerge the bottle opening downward below the water surface, positioning it into the prevailing current, and fill by scooping in an upstream direction. Crucially, minimize disturbance of bottom sediments and avoid collecting water containing resuspended sediment. When sampling from a boat, carefully reach over the upstream side. Plunge the bottle below the surface, turn it into the current away from your body, and fill until only a one-inch air space remains (note: this air space exclusion applies to all samples except those for Dissolved Oxygen (DO) or Biochemical Oxygen Demand (BOD)); do not fill the bottle to allow for shaking before analysis. After collection, carefully recap the bottle without touching the interior surface. Record the bottle number and/or site number in the designated field data sheet. For samples requiring laboratory analysis, place them immediately into a cooler for transport. Throughout this process, wading is prohibited, and vigilance against sediment disturbance is essential.

For Whirl- Park Bags

Before sampling, the sample bag is clearly labeled with the site number, date, and time. Immediately before collection, tear the bag along the perforation above the wire tab while rigorously avoiding contact with the interior surface; discard and replace the bag if accidental interior contact occurs. Prohibit wading during this process. Position yourself facing upstream when collecting from shore, or carefully reach over the upstream side of a boat when sampling from a vessel. Minimize disturbance of bottom sediments and ensure collected water is free of resuspended substrate. Hold the two white pull tabs and submerge the bag with its opening oriented upstream. Midway between the water surface and bottom, open the bag by pulling the white tabs outward, allowing it to fill naturally. Fill the bag to no more than three-quarters capacity. Retrieve the bag promptly, pour out excess water, and securely close it by pulling the wire tabs. Maintain grip on the wire tabs and invert the bag rapidly 4 - 5 times to affect a seal; do not compress air from the top. Fold the wire tab ends together at the bag’s apex without puncturing the material, twist them to form a loop, and record the bag number and/or site number on the designated field data sheet. This labeling step is critical for laboratory sample identification. Finally, place samples designated for laboratory analysis immediately into a cooler containing ice or cold packs to preserve integrity during transport.

Results

The levels of heavy metal concentrations in the water samples are presented in the tables below.

Table 1: Metal concentration: Aluminum, Arsenic, Calcium, Cadmium, Cobalt, and Chromium Heavy metals concentrations

*WHO = WHO Acceptable Limit Mg/L (2003), NP = No Value is proposed, NG = Not mentioned in the WHO Guideline. SP1. Egboha River – Edo State; SP2. Itu River – Awa – Ibom State; SP3. Tap Water – Iginedion University, Okada, Edo State; SP4. Obaretin River – Edo State; SP5. Akpabuyo River – Cross River State; SP6. Ologbo River – Edo State; SP7. Okponha River – Edo State; SP8. Usen River – Edo State; SP9. Nsit Ubium River – Akwa-Ibom State; SP10. Nsit Ibom River –Akwa-Ibom State; SP11. Esuk Nsidung – Cross River State; SP12. Delta state, SP13. Okada River – Edo State.

Table 2: Metal concentration: Copper, Iron, Potassium, Magnsium, and Manganese Heavy metals concentrations

*NV =Normal Values, NH = Not of health concern at levels found in drinking water.

Table 3: Metal concentration: Sodium, Lead, and Zinc Heavy metals concentrations

Discussion

From the results shown, Manganese, chromium, and lead limits are normal. As depicted in the table above, elements such as arsenic had concentrations slightly above the WHO (2003) allowable limit in SP4, SP11, and SP13. High concentrations of heavy metals and other elements in the river must have occurred as a result of contaminated soil or pollution of the water with dirt. Levels of heavy metals in other areas of Edo State, Cross-river and Akwa-Ibom State are relatively safe. Despite existing measures, State Governments' appropriate agencies must implement proactive interventions to ensure the potability of community drinking water sources. Acute exposure to contaminants can induce severe gastrointestinal distress, including nausea, anorexia, vomiting, abdominal pain, and diarrhea, alongside neuromuscular manifestations such as muscle cramps, oropharyngeal irritation, including burning of the mouth and throat.

Paradoxically, magnesium, a mineral abundantly sourced from dietary components such as fruits, dark leafy vegetables, legumes, nuts, whole grains, seeds, and soy products, serves as a critical cofactor for numerous vital physiological functions. Approximately 87% of the body's magnesium reserves are sequestered within skeletal structures and muscular tissues, where it facilitates indispensable metabolic and enzymatic processes fundamental to human physiology [26,27].

The human body depends on adenosine triphosphate, or ATP, as a source of energy. The body breaks down food consumed into ATP by a series of complex metabolic reactions. The energy-producing mitochondria in cells contain proteins that produce ATP. These proteins require magnesium to create new ATP molecules. ATP forms a chelate, or bonded complex, with magnesium in cells. Thus, magnesium is essential for basic cellular activities that require ATP. Over 300 metabolic reactions depend on the presence of magnesium [28,29].

Numerous physiological processes depend critically upon the regulated transmembrane movement of ions. Specialized ion pumps actively transport potassium (K+), calcium (Ca²+), sodium (Na+), and other ions across the cellular membrane. This mechanism enables the cellular accumulation of essential ions required for fundamental biological activities, including skeletal and cardiac muscle contraction, neuronal signal transmission, and the maintenance of regular cardiac rhythm. Consequently, magnesium (Mg²+) serves as an indispensable mineral cofactor, facilitating the transport of these ions into and out of cells and thereby underpinning these vital physiological functions [30-32].

Also, several nutrients affect the dietary absorption of magnesium. The presence of vitamin D increases the rate of absorption of magnesium from the intestines. Increasing daily protein intake may also improve the absorption of magnesium. However, boosting Zinc levels through supplements interferes with the body’s ability to effectively absorb magnesium.

The recommended dietary allowance of magnesium in infants: from 50 – 75mg per day; children: 80 – 240mg per day, depending on their age; male adults: 400 – 420mg daily; female adults: 310 – 320mg daily; and in a pregnant female adult, it should be increased to 350 – 400mg per day [33]. Failing to consume enough magnesium may lead to serious health effects. Initial manifestations of magnesium deficiency encompass neurological and neuromuscular disturbances, including confusion, apathy, fatigue, mild muscular fasciculations, insomnia, irritability, and impaired recall. Progression to severe deficiency induces pronounced neuromuscular hyperexcitability, characterized by numbness, paresthesia (tingling sensations), severe muscle contractions, and altered mental status, notably delirium and hallucinations [34-36].

Arsenic trioxide received approval from the Food and Drug Administration in 2000 for treating acute promyelocytic leukemia [37]. and was historically employed as Fowler’s solution against psoriasis [38]. While arsenic's precise physiological role remains undefined, certain bacteria derive energy by oxidizing fuels and reducing arsenate to arsenite. Evidence indicates that arsenic intake influences plasma and tissue concentrations of taurine and polyamines [39]. Specifically, arsenic deprivation in rats and hamsters decreases plasma taurine, reduces hepatic polyamine concentrations, and lowers the specific activity of S-adenosyl methionine decarboxylase, an enzyme critical for synthesizing spermidine and spermine. This evidence underscores arsenic's physiological significance, particularly under conditions of methionine metabolism stress, such as pregnancy, lactation, methionine deficiency, or vitamin B6 deprivation [40,41]. Human nutritional requirements for arsenic can only be extrapolated from animal studies, suggesting a level near 25 ng g-¹ diet for growing chicks and rats, implying a potential human requirement of approximately 12 µg day¹ [40]. Chromium facilitates insulin-mediated glucose transport into cells and participates in the metabolism of carbohydrates, proteins, and fats [42]. It functions by bridging insulin to cellular insulin receptors, thereby modulating cellular glucose uptake and the utilization of carbohydrates and lipids [43]. Inadequate chromium intake correlates with glucose intolerance, impairing efficient cellular glucose use, and it also participates in fat metabolism, potentially offering protection against heart disease [44]. Manganese acts as an essential cofactor for enzymes involved in hydrolysis, phosphorylation, decarboxylation, and transamination [45] and enhances the activity of transferases, including glycosyl transferase, glutamine synthetase, and superoxide dismutase. It further supports enzyme production for protein and fat metabolism, immune function, blood sugar regulation, cellular energy production, reproductive processes, and bone growth [46]. Calcium serves as a primary structural component in bones and teeth, predominantly within hydroxyapatite (Ca10(PO4)6(OH)2) crystals, which incorporate substantial calcium and phosphate [47]. Beyond its structural role, calcium mediates vasoconstriction and vasodilation, nerve impulse transmission, muscle contraction, and hormone secretion, such as insulin [48], and stabilizes numerous enzymes and proteins as a cofactor, optimizing their activity [49]. Sodium regulates bodily fluid balance and is crucial for nerve transmission and muscle contraction [50]. In contrast, no physiological function has been established for aluminum, though its frequent exposure is associated with neurotoxicity [51,52]. Zinc is essential for human growth, reproduction, and the functionality of over 300 enzymes; it also stabilizes DNA and regulates gene expression [53]. Potassium is indispensable for maintaining fluid homeostasis, nerve impulse conduction, muscle function, and cardiac activity [54].

Research indicates that one-third of tested products contained at least one toxic metal at levels deemed hazardous, with many samples exhibiting the presence of multiple toxic metals, thereby increasing the potential for harm. None of these contaminated items carried warning labels to inform consumers of their toxic content. Toys tested were found to contain heavy metals, including lead, a substance especially harmful to children, yet such products remain available on the market [55]. Studies show that infants and children face disproportionately high exposure to environmental agents due to their higher intake of water and air relative to body weight, immature metabolic systems, particularly in fetal and early postnatal life, and the vulnerability of developmental processes during periods of rapid growth. Additionally, children’s longer life expectancy gives more time for diseases initiated by early exposures to develop [56,57].

Inorganic arsenic, a known human carcinogen, is linked to cancers of the lung, skin, and bladder and has been associated with reduced IQ in children [58]. Cadmium, also classified as a human carcinogen, is linked to cancers of the breast, kidney, lung, pancreas, prostate, and bladder [59]. Chromium VI has been found to cause cancer in humans and is associated in laboratory studies with birth defects and reproductive problems. Lead is a recognized neurotoxicant with no established safe exposure level, and its detrimental effects on children, including cognitive impairments, attention deficits, coordination problems, and anemia, are irreversible and persist into adolescence and adulthood [60-63]. Mercury, another potent neurotoxicant, poses significant risks to the developing nervous system, and exposure can result in IQ loss, muscle tone abnormalities, motor dysfunction, attention deficits, and impaired visual-spatial skills [64].

Lead ingestion is the leading cause of heavy metal poisoning in children. In 2000, it was estimated that one in every 22 American children had elevated blood lead levels. Children in urban settings with aging lead plumbing and lead-painted homes are particularly vulnerable [65]. Symptoms of heavy metal poisoning vary depending on the specific metal and amount ingested, potentially including nausea, vomiting, diarrhea, abdominal pain, headache, sweating, and a metallic taste. Some individuals may display black lines along the gum tissue [66]. Diagnosis of heavy metal poisoning can involve blood and urine testing, hair and tissue analysis, or X-rays. In children, blood lead levels above 80 mg/dL typically indicate poisoning, with the Centers for Disease Control and Prevention flagging levels of 10 mg/dL or higher as concerning. Blood mercury levels should remain below 3.6 mg/dL, and urine mercury levels should not exceed 15 mg/dL. Due to its rapid clearance from the bloodstream, arsenic levels in blood are not always useful for diagnosis [67,68].

Cadmium toxicity is usually indicated when urine levels exceed 10 mg/dL of creatinine or blood levels surpass 5 mg/dL. Chelation therapy is the standard treatment for most heavy metal poisoning, involving the administration of a chelating agent, such as calcium disodium edetate, dimercaprol, or penicillamine, either orally, intramuscularly, or intravenously [69,70].  The chelating agent binds to the metal in body tissues, forming a complex that is transported in the bloodstream, filtered by the kidneys, and eliminated through urine. This process is often painful and lengthy, typically requiring hospitalization. While chelation therapy is effective for lead, mercury, and arsenic poisoning, it is not suitable for cadmium [71,72].   In cases of arsenic ingestion, inducing vomiting or gastric lavage may be employed. However, chelation only halts further toxic effects and cannot reverse neurological damage already sustained. To protect children’s health, exposure to environmental lead sources, such as lead-based paint, plumbing fixtures, vehicle emissions, and contaminated soil, must be minimized or eliminated [73,74].

Ensuring the safety of children's products primarily falls on manufacturers, who must eliminate toxic substances like lead from their products by improving production processes and disclosing chemical ingredients. Government agencies should enforce stricter protective standards for lead and apply comprehensive limits to other heavy metals. Consumers are urged to read safety labels carefully before making purchases and to advocate for stringent regulations that limit toxic materials in consumer products.

Table 4: Absorption wavelength for the detection of heavy metals using AAS from the different sites

Table 4 presents the absorption wavelengths used for the detection of various heavy metals through Atomic Absorption Spectroscopy (AAS) from different sampling sites. Each metal has a characteristic wavelength where maximum absorption occurs, allowing for accurate qualitative and quantitative analysis. The elements such as Na (589.59 nm) and K (766.49 nm) are major alkali metals and are typically present in higher concentrations, serving as indicators of geochemical and anthropogenic inputs. Transition metals such as Cu (327.39 nm), Fe (238.20 nm), Mn (257.61 nm), and Zn (206.20 nm) are essential trace elements but can become toxic at elevated levels. Toxic heavy metals, including Pb (220.35 nm), Cd (228.80 nm), and Cr (267.71 nm), are of particular environmental concern due to their persistence and potential bioaccumulation.

The variation in absorption wavelengths highlights the specificity of AAS for detecting each element with minimal spectral interference. This ensures precise monitoring of contamination across different sites. The selection of these wavelengths is crucial for achieving maximum sensitivity and reducing detection limits, thereby improving the reliability of the heavy metal assessment in environmental samples.

Conclusion

This comprehensive assessment of heavy metals in Southern Nigerian water sources demonstrates that while many analytes, such as Cd, Cr, Pb, and Mn, generally adhere to WHO guidelines at most sampling sites, significant arsenic exceedances in Edo (SP4, SP13) and Cross River (SP11) demand urgent attention. These elevated levels likely stem from geogenic processes or anthropogenic pollution, such as industrial runoff, oil exploration, or agricultural leaching, necessitating source identification and mitigation. The rigorous sampling protocol, prioritizing mid-current collection and stringent container preparation, ensured data reliability, while the use of ICP-OES provided robust multi-element detection with minimal interference. The health implications of arsenic exposure are severe, including lung, skin, bladder cancers, and developmental deficits in children. Lead, though largely within limits here, remains a critical concern due to its irreversible neurotoxic impacts, especially in urban areas with aging infrastructure. Notably, children are disproportionately vulnerable to heavy metals due to higher intake per body weight, hand-to-mouth behaviors, and developing physiological systems. This study also contextualizes essential elements like magnesium (vital for ATP metabolism) and chromium (key to glucose regulation), emphasizing that both deficiency and excess of metals like arsenic pose complex public health challenges. Spatially, Edo State emerged as a hotspot for contamination of aluminum in SP4, SP8, SP10, and arsenic in SP4/SP13, warranting prioritized intervention. Akwa-Ibom and Cross River showed localized risks of arsenic in SP11, but overall lower metal burdens. Regulatory failures exacerbate these risks, as evidenced by undocumented toxins in consumer goods and inadequate safety labeling. To address this, manufacturers must eliminate hazardous materials from products, while governments should enforce stricter total concentration limits for heavy metals beyond lead. Future research should quantify pollution sources, such as isotopic tracing, to assess seasonal variations and evaluate remediation techniques like chelation-enhanced phytoremediation.

References

1. BUNU, SAMUEL J., DORATHY GEORGE, D. E. G. H. I. N. M. O. T. E. I. ALFRED-UGBENBO, and BENJAMIN U. EBESHI. "Heavy metals quantification and correlative carcinogenic-risks evaluation in selected energy drinks sold in Bayelsa state using atomic absorption spectroscopic technique." International Journal of Chemistry Research (2023): 1-4.
   View at Publisher | View at Google Scholar
2. Jovita, Onyeukwu Nkechi, Urua Scholastica Patrick, Awala Victoria Ebisindor, Bunu Samuel Jacob, Onwuka Ngozi, and Osom Unwana Akpan Amanda. "Heavy Metals Health-Risk Assessment of Zingiber officinale in Akwa Ibom and Enugu following High Consumption During the COVID-19 Era." (2025).
   View at Publisher | View at Google Scholar
3. Jovita, Onyeukwu Nkechi, Okonkwo Ogochukwu Emmanuel, Osom Unwana Akpan, Anah Victor Udoh, and Bunu Samuel Jacob. "Health-Risk Assessment of Heavy Metals in Drinking Water Obtained from Public Primary Schools in Akwa Ibom State, Nigeria." Sch Acad J Pharm 3 (2025): 42-50.
   View at Publisher | View at Google Scholar
4. Garrigues, Salvador, and Miguel de la Guardia, eds. Challenges in green analytical chemistry. Vol. 66. Royal Society of Chemistry, 2020.
   View at Publisher | View at Google Scholar
5. Kobayashi, Norihiro. "Development of Sensitive and Specific Determination Methods of Bioactive Compounds Based on Generation of High-Performance Antibodies." Biological and Pharmaceutical Bulletin 48, no. 5 (2025): 475-494.
   View at Publisher | View at Google Scholar
6. Bunu, Samuel J., Edebi N. Vaikosen, and Kosi W. Nnadozie. "Chloroquine phosphate metabolism and gender-based phenotypic analysis in healthy subjects’ urine following oral administration." Pharmaceutical and Biomedical Research 6 (2020): 37-44.
   View at Publisher | View at Google Scholar
7. Samuel, Bunu J., Ere Diepreye, and Wilson O. Diana. "Simple thin-layer chromatographic and UV-spectrophotometric analysis of Promethazine and its N-demethylation metabolites from biological fluids." International Journal of PharmTech Research 13, no. 04 (2020): 316-324.
   View at Publisher | View at Google Scholar
8. Nwankwo, Ogechukwu L., Onwuzuluigbo C. Chukwuebuka, Okeke O. Collins, Bunu J. Samuel, Josephat C. Obasi, Ezinne S. Iloh, and Emmanuel Okechukwu Nwankwo. "Quantitative phytochemical analysis of the fungus endophytic extracts isolated from Azadirachta indica using gas chromatography-flame ionization detector." Journal of Drug Delivery and Therapeutics 11, no. 5 (2021): 80-83.
   View at Publisher | View at Google Scholar
9. Ebeshi BU, Bunu SJ, Vaikosen NE, Kashimawo JA, Kpun HF, Okpareke D (2022). Physicochemical Analysis and Thin-Layer Chromatographic Fingerprinting of Some Beta-Lactam Antibiotics. International Journal of Pharmaceutical Research and Applications, 7 (3), 961-967.
   View at Publisher | View at Google Scholar
10. Jones, Matthew R., Rosie Chance, Ruzica Dadic, Henna-Reetta Hannula, Rebecca May, Martyn Ward, and Lucy J. Carpenter. "Environmental iodine speciation quantification in seawater and snow using ion exchange chromatography and UV spectrophotometric detection." Analytica Chimica Acta (2023).
    View at Publisher | View at Google Scholar
11. Havezov, I. "Atomic absorption spectrometry (AAS)–a versatile and selective detector for trace element speciation." Fresenius' journal of analytical chemistry 355, no. 5 (1996): 452-456.
    View at Publisher | View at Google Scholar
12. Wilson, A. Matthew, Phillip J. Bailey, Peter A. Tasker, Jennifer R. Turkington, Richard A. Grant, and Jason B. Love. "Solvent extraction: the coordination chemistry behind extractive metallurgy." Chemical Society Reviews 43, no. 1 (2014): 123-134.
    View at Publisher | View at Google Scholar
13. Zolotov, Yu A., E. I. Morosanova, S. G. Dmitrienko, A. A. Formanovsky, and G. V. Ivanov. "Solvent extraction of metals with macrocyclic compounds. II: The use of 19-membered compounds with donor systems 2N, 20 and 2N, 30." Microchimica Acta 84, no. 5 (1984): 399-408.
    View at Publisher | View at Google Scholar
14. Douvris, Chris, Trey Vaughan, Derek Bussan, Georgios Bartzas, and Robert Thomas. "How ICP-OES changed the face of trace element analysis: Review of the global application landscape." Science of The Total Environment 905 (2023): 167242.
    View at Publisher | View at Google Scholar
15. Ready, Joseph, and Callie Seaman. "Laser Ablation Inductively Coupled Plasma Mass Spectrometry Imaging of Plant Materials." In Imaging Mass Spectrometry: Methods and Protocols, pp. 123-133. New York, NY: Springer US, 2023.
    View at Publisher | View at Google Scholar
16. Makonnen, Yoseif, and Diane Beauchemin. "The inductively coupled plasma as a source for optical emission spectrometry and mass spectrometry." In Sample Introduction Systems in ICPMS and ICPOES, pp. 1-55. Elsevier, 2020.
    View at Publisher | View at Google Scholar
17. DeSousa, Jenna M., Micaella Z. Jorge, Hayley B. Lindsay, Frederick R. Haselton, David W. Wright, and Thomas F. Scherr. "Inductively coupled plasma optical emission spectroscopy as a tool for evaluating lateral flow assays." Analytical Methods 13, no. 18 (2021): 2137-2146.
    View at Publisher | View at Google Scholar
18. Khan, Sharib Raza, Babita Sharma, Pooja A. Chawla, and Rohit Bhatia. "Inductively coupled plasma optical emission spectrometry (ICP-OES): a powerful analytical technique for elemental analysis." Food Analytical Methods 15, no. 3 (2022): 666-688.
    View at Publisher | View at Google Scholar
19. Jin, Mengting, Hao Yuan, Bo Liu, Jiajia Peng, Liping Xu, and Dezheng Yang. "Review of the distribution and detection methods of heavy metals in the environment." Analytical methods 12, no. 48 (2020): 5747-5766.
    View at Publisher | View at Google Scholar
20. Gong, Zhaoyuan, Hiu Ting Chan, Qilei Chen, and Hubiao Chen. "Application of nanotechnology in analysis and removal of heavy metals in food and water resources." Nanomaterials 11, no. 7 (2021): 1792.
    View at Publisher | View at Google Scholar
21. Kannan, Prashanth, Ajay Narayan Konda Ravindranath, Sunil Suresh Domala, Mitko Oldfield, Agustin Schiffrin, and Dipti Gupta. "Tripartite Detection and Sensing of Toxic Heavy Metals Using a Copper-Based Porphyrin Metal–Organic Framework." ACS applied materials & interfaces 16, no. 46 (2024): 64166-64176.
    View at Publisher | View at Google Scholar
22. Bulska, Ewa, and Barbara Wagner. "Quantitative aspects of inductively coupled plasma mass spectrometry." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 374, no. 2079 (2016): 20150369.
    View at Publisher | View at Google Scholar
23. Van Acker, Thibaut, Sarah Theiner, Eduardo Bolea-Fernandez, Frank Vanhaecke, and Gunda Koellensperger. "Inductively coupled plasma mass spectrometry." Nature Reviews Methods Primers 3, no. 1 (2023): 52.
    View at Publisher | View at Google Scholar
24. Bunu, Samuel J., Benjamin U. Ebeshi, Hilda F. Kpun, Adesegun J. Kashimawo, Edebi N. Vaikosen, and Chubiyojo B. Itodo. "Atomic absorption spectroscopic (AAS) analysis of heavy metals and health risks assessment of some common energy drinks." Pharmacology and Toxicology of Natural Medicines (ISSN: 2756-6838) 3, no. 1 (2023): 1-10.
    View at Publisher | View at Google Scholar
25. Svehla, Gyula. Vogel's qualitative inorganic analysis, 7/e. Pearson Education India, 2008.
    View at Publisher | View at Google Scholar
26. Long, Samantha, and Andrea MP Romani. "Role of cellular magnesium in human diseases." Austin journal of nutrition and food sciences 2, no. 10 (2014): 1051.
    View at Publisher | View at Google Scholar
27. Fatima, Ghizal, Andrej Dzupina, Hekmat B. Alhmadi, Aminat Magomedova, Zainab Siddiqui, Ammar Mehdi, Najah Hadi, and AMMAR MEHDI RAZA. "Magnesium matters: A comprehensive review of its vital role in health and diseases." Cureus 16, no. 10 (2024).
    View at Publisher | View at Google Scholar
28. Ko, Young Hee, Sangjin Hong, and Peter L. Pedersen. "Chemical mechanism of ATP synthase: magnesium plays a pivotal role in formation of the transition state where ATP is synthesized from ADP and inorganic phosphate." Journal of Biological Chemistry 274, no. 41 (1999): 28853-28856.
    View at Publisher | View at Google Scholar
29. Buelens, Floris P., Hadas Leonov, Bert L. de Groot, and Helmut Grubmüller. "ATP–magnesium coordination: protein structure-based force field evaluation and corrections." Journal of Chemical Theory and Computation 17, no. 3 (2021): 1922-1930.
    View at Publisher | View at Google Scholar
30. Vormann, Jürgen. "Magnesium: nutrition and homoeostasis." AIMS public health 3, no. 2 (2016): 329.
    View at Publisher | View at Google Scholar
31. Kulbacka, Julita, Anna Choromańska, Joanna Rossowska, Joanna Weżgowiec, Jolanta Saczko, and Marie-Pierre Rols. "Cell membrane transport mechanisms: ion channels and electrical properties of cell membranes." Transport across natural and modified biological membranes and its implications in physiology and therapy (2017): 39-58.
    View at Publisher | View at Google Scholar
32. Fiorentini, Diana, Concettina Cappadone, Giovanna Farruggia, and Cecilia Prata. "Magnesium: biochemistry, nutrition, detection, and social impact of diseases linked to its deficiency." Nutrients 13, no. 4 (2021): 1136.
    View at Publisher | View at Google Scholar
33. USA National Research Council (1989). National Research Council (US) Subcommittee on the Tenth Edition of the Recommended Dietary Allowances. Recommended Dietary Allowances: 10th Edition. Washington (DC): National Academies Press (US); 1989. 1. Summary. Available from: https://www.ncbi.nlm.nih.gov/books/NBK234929/
    View at Publisher | View at Google Scholar
34. Elin, Ronald J. "Assessment of magnesium status for diagnosis and therapy." Magnesium research 23, no. 4 (2010): 194-198.
    View at Publisher | View at Google Scholar
35. Kass, Lindsy, J. Weekes, and Lewis Carpenter. "Effect of magnesium supplementation on blood pressure: a meta-analysis." European journal of clinical nutrition 66, no. 4 (2012): 411-418.
    View at Publisher | View at Google Scholar
36. Kass, Lindsy, J. Weekes, and Lewis Carpenter. "Effect of magnesium supplementation on blood pressure: a meta-analysis." European journal of clinical nutrition 66, no. 4 (2012): 411-418.
    View at Publisher | View at Google Scholar
37. Xu, ShuangNian, JiePing Chen, Jian Ping Liu, Yun Xia, Xi Li, and Ya Tan. "Arsenic trioxide for the treatment of acute promyelocytic leukaemia." The Cochrane Database of Systematic Reviews 2016, no. 12 (2016): CD008425.
    View at Publisher | View at Google Scholar
38. Ho, Derek, and Eve J. Lowenstein. "Fowler's Solution and the Evolution of the Use of Arsenic in Modern Medicine." Skinmed 14, no. 4 (2016): 287-289.
    View at Publisher | View at Google Scholar
39. Jurtshuk, Peter. "Bacterial metabolism." Medical microbiology 4 (1996).
    View at Publisher | View at Google Scholar
40. Uthus, Eric O. "Evidence for arsenic essentiality." Environmental Geochemistry and Health 14, no. 2 (1992): 55-58.
    View at Publisher | View at Google Scholar
41. Koike, Shinichiro, Yukihito Kabuyama, Kodwo Amuzuah Obeng, Kunio Sugahara, Yusuke Sato, and Fumiaki Yoshizawa. "An increase in liver polyamine concentration contributes to the tryptophan-induced acute stimulation of rat hepatic protein synthesis." Nutrients 12, no. 9 (2020): 2665.
    View at Publisher | View at Google Scholar
42. Zhang, Weijie, Hui Chen, Yangyang Ding, Qingfang Xiang, Jie Zhao, Weiwei Feng, and Liuqing Yang. "Effect of chromium citrate on the mechanism of glucose transport and insulin resistance in Buffalo rat liver cells." Indian Journal of Pharmacology 52, no. 1 (2020): 31-38.
    View at Publisher | View at Google Scholar
43. Vincent, J. B., & Lukaski, H. C. (2018). Chromium. Advances in nutrition (Bethesda, Md.), 9(4), 505–506. https://doi.org/10.1093/advances/nmx021.
    View at Publisher | View at Google Scholar
44. Haider, Ali Murtaza, Arsalan Ali, Ebraheem Abdu Musad Saleh, Abduladheem Turki Jalil, Furqan M. Abdulelah, Rosario Mireya Romero-Parra, Nahla A. Tayyib, Andrés Alexis Ramírez-Coronel, and Ameer S. Alkhayyat. "The role of chromium supplementation in cardiovascular risk factors: A comprehensive reviews of putative molecular mechanisms." Heliyon 9, no. 9 (2023).
    View at Publisher | View at Google Scholar
45. Chen, Pan, Julia Bornhorst, and Michael Aschner. "Manganese metabolism in humans." Front Biosci (Landmark Ed) 23, no. 9 (2018): 1655-1679.
    View at Publisher | View at Google Scholar
46. Li, Longman, and Xiaobo Yang. "The essential element manganese, oxidative stress, and metabolic diseases: links and interactions." Oxidative medicine and cellular longevity 2018, no. 1 (2018): 7580707.
    View at Publisher | View at Google Scholar
47. Bonjour, Jean-Philippe. "Calcium and phosphate: a duet of ions playing for bone health." Journal of the American College of Nutrition 30, no. sup5 (2011): 438S-448S.
    View at Publisher | View at Google Scholar
48. Amberg, Gregory C., and Manuel F. Navedo. "Calcium dynamics in vascular smooth muscle." Microcirculation 20, no. 4 (2013): 281-289.
    View at Publisher | View at Google Scholar
49. Bootman, Martin D., and Geert Bultynck. "Fundamentals of cellular calcium signaling: a primer." Cold Spring Harbor perspectives in biology 12, no. 1 (2020): a038802.
    View at Publisher | View at Google Scholar
50. Bernal, Antonio, María A. Zafra, María J. Simón, and Javier Mahía. "Sodium homeostasis, a balance necessary for life." Nutrients 15, no. 2 (2023): 395.
    View at Publisher | View at Google Scholar
51. Kumar, Vijay, and Kiran Dip Gill. "Aluminium neurotoxicity: neurobehavioural and oxidative aspects." Archives of toxicology 83, no. 11 (2009): 965-978.
    View at Publisher | View at Google Scholar
52. Klotz, Katrin, Wobbeke Weistenhöfer, Frauke Neff, Andrea Hartwig, Christoph van Thriel, and Hans Drexler. "The health effects of aluminum exposure." Deutsches Ärzteblatt International 114, no. 39 (2017): 653.
    View at Publisher | View at Google Scholar
53. Kiouri, Despoina P., Evi Tsoupra, Massimiliano Peana, Spyros P. Perlepes, Maria E. Stefanidou, and Christos T. Chasapis. "Multifunctional role of zinc in human health: an update." EXCLI journal 22 (2023): 809.
    View at Publisher | View at Google Scholar
54. Gumz, Michelle L., Lawrence Rabinowitz, and Charles S. Wingo. "An integrated view of potassium homeostasis." New England Journal of Medicine 373, no. 1 (2015): 60-72.
    View at Publisher | View at Google Scholar
55. Yoshinaga, Jun. "Lead in the Japanese living environment." Environmental health and preventive medicine 17, no. 6 (2012): 433-443.
    View at Publisher | View at Google Scholar
56. Carroquino, Maria J., M. Posada, and P. J. Landrigan. "Environmental toxicology: children at risk." In Environmental toxicology: selected entries from the encyclopedia of sustainability science and technology, pp. 239-291. New York, NY: Springer New York, 2012.
    View at Publisher | View at Google Scholar
57. Hauptman, Marissa, and Alan D. Woolf. "Childhood ingestions of environmental toxins: what are the risks?." Pediatric annals 46, no. 12 (2017): e466-e471.
    View at Publisher | View at Google Scholar
58. Speer, Rachel M., Xixi Zhou, Lindsay B. Volk, Ke Jian Liu, and Laurie G. Hudson. "Arsenic and cancer: Evidence and mechanisms." In Advances in pharmacology, vol. 96, pp. 151-202. Academic Press, 2023.
    View at Publisher | View at Google Scholar
59. Huff, James, Ruth M. Lunn, Michael P. Waalkes, Lorenzo Tomatis, and Peter F. Infante. "Cadmium-induced cancers in animals and in humans." International journal of occupational and environmental health 13, no. 2 (2007): 202-212.
    View at Publisher | View at Google Scholar
60. Costa, Max. "Toxicity and carcinogenicity of Cr (VI) in animal models and humans." Critical reviews in toxicology 27, no. 5 (1997): 431-442.
    View at Publisher | View at Google Scholar
61. Wilbur S, Abadin H, Fay M, Yu D, Tencza B, Ingerman L, Klotzbach J, & James S. (2012). Toxicological Profile for Chromium. Agency for Toxic Substances and Disease Registry (US).
    View at Publisher | View at Google Scholar
62. Delgado, Christine F., Mary Anne Ullery, Melissa Jordan, Chris Duclos, Sudha Rajagopalan, and Keith Scott. "Lead exposure and developmental disabilities in preschool-aged children." Journal of public health management and practice 24, no. 2 (2018): e10-e17.
    View at Publisher | View at Google Scholar
63. Ramírez Ortega, Daniela, Dinora F. González Esquivel, Tonali Blanco Ayala, Benjamín Pineda, Saul Gómez Manzo, Jaime Marcial Quino, Paul Carrillo Mora, and Verónica Pérez de la Cruz. "Cognitive impairment induced by lead exposure during lifespan: mechanisms of lead neurotoxicity." Toxics 9, no. 2 (2021): 23.
    View at Publisher | View at Google Scholar
64. Branco, Vasco, Michael Aschner, and Cristina Carvalho. "Neurotoxicity of mercury: an old issue with contemporary significance." In Advances in neurotoxicology, vol. 5, pp. 239-262. Academic Press, 2021.
    View at Publisher | View at Google Scholar
65. Mitra, Prasenjit, Shailja Sharma, Purvi Purohit, and Praveen Sharma. "Clinical and molecular aspects of lead toxicity: An update." Critical reviews in clinical laboratory sciences 54, no. 7-8 (2017): 506-528.
    View at Publisher | View at Google Scholar
66. Kim, Nam Hee, Young Youl Hyun, Kyu-Beck Lee, Yoosoo Chang, Seungho Rhu, Kook-Hwan Oh, and Curie Ahn. "Environmental heavy metal exposure and chronic kidney disease in the general population." Journal of Korean medical science 30, no. 3 (2015): 272.
    View at Publisher | View at Google Scholar
67. Binns, Helen J., Carla Campbell, Mary Jean Brown, and Advisory Committee on Childhood Lead Poisoning Prevention. "Interpreting and managing blood lead levels of less than 10 μg/dL in children and reducing childhood exposure to lead: Recommendations of the Centers for Disease Control and Prevention Advisory Committee on Childhood Lead Poisoning Prevention." Pediatrics 120, no. 5 (2007): e1285-e1298.
    View at Publisher | View at Google Scholar
68. Bolan, Shiv, Anitha Kunhikrishnan, Balaji Seshadri, Girish Choppala, Ravi Naidu, Nanthi S. Bolan, Yong Sik Ok et al. "Sources, distribution, bioavailability, toxicity, and risk assessment of heavy metal (loid) s in complementary medicines." Environment international 108 (2017): 103-118.
    View at Publisher | View at Google Scholar
69. Vacchi-Suzzi, Caterina, Danielle Kruse, James Harrington, Keith Levine, and Jaymie R. Meliker. "Is urinary cadmium a biomarker of long-term exposure in humans? A review." Current environmental health reports 3, no. 4 (2016): 450-458.
    View at Publisher | View at Google Scholar
70. Rahimzadeh, Mehrdad Rafati, Mehravar Rafati Rahimzadeh, Sohrab Kazemi, and Ali-akbar Moghadamnia. "Cadmium toxicity and treatment: An update." Caspian journal of internal medicine 8, no. 3 (2017): 135.
    View at Publisher | View at Google Scholar
71. Flora, Swaran JS, and Vidhu Pachauri. "Chelation in metal intoxication." International journal of environmental research and public health 7, no. 7 (2010): 2745-2788.
    View at Publisher | View at Google Scholar
72. Entezari, Sarina, Seyedeh Mona Haghi, Narges Norouzkhani, Barsa Sahebnazar, Fatemeh Vosoughian, Diba Akbarzadeh, Muhammad Islampanah, Navid Naghsh, Mohammad Abbasalizadeh, and Niloofar Deravi. "Iron chelators in treatment of iron overload." Journal of toxicology 2022, no. 1 (2022): 4911205.
    View at Publisher | View at Google Scholar
73. Olsen V, & Mørland J. (2004). Forgiftning med arsen [Arsenic poisoning]. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 124(21), 2750–2753.
    View at Publisher | View at Google Scholar
74. Martínez-Castillo, Macario, Eliud A. García-Montalvo, Mónica G. Arellano-Mendoza, Luz del C. Sánchez-Peña, Luis E. Soria Jasso, Jeannett A. Izquierdo-Vega, Olga L. Valenzuela, and Araceli Hernández-Zavala. "Arsenic exposure and non-carcinogenic health effects." Human & Experimental Toxicology 40, no. 12_suppl (2021): S826-S850.
    View at Publisher | View at Google Scholar