1. INTRODUCTION:

Pharmaceuticals are physiologically active chemicals that are intended to start a biological process in the bodies of people or animals and are often active at extremely low doses; these can cause disruptions in soil functionality and limit plant development¹. However, antibiotic pollution puts everyone at danger, regardless of where they live, consequent to the way that antibiotic manufacturing emissions generate resistance in bacteria that are already present in the environment, spreading to human diseases². Subsequently, ecotoxicologists who were focused mostly on sewage effluents, receiving rivers, which may have diverted attention from potential alternate sources of pharmaceutical residues³. If manufacturing discharges are considered as a whole, a greater number of APIs should experience unfavourable environmental concentrations⁴.

The new analytical tools can now detect pharmaceuticals at all levels present in the nature has caused some recent concern^5,6.

2. Pharmaceutials infiltration in Environment:

They comes in the atmosphere through different channels. The ingestion (excretion) route is typically cited as extensive route, but improper disposal of pharmaceutical waste also plays a substantial role; These are some examples of infiltration: Through manufacture, Through consumption and Waste. Pharmaceuticals can be eliminated through waste treatment⁷.

2.1 Manure and animal effluent:

The agricultural soil and consequently in vegetables and run-off into surface waters, are caused by the application of manure and slurry to farms. The only area of the veterinary medication business that is developing is companion animal therapies, although pet faeces and urine are also a growing problem.

2.2 Unsuitable disposable of unwanted medications: Over-the-counter medications are frequently purchased in excess and come in standard-sized packs that may not contain all that is required. The patient's perception that the ailment is cured, real or imagined adverse responses, or a change in treatment; so, all these conditions getting worse could all contribute to this.

2.3 Residue limitations and monitoring information: Neither the statutory nor the private sectors have many systematic monitoring programmes, nor are there many regulatory limits defined for pharmaceutical residues⁸.

3. Demands placed on analytical test methods: Because there are so many possible pollutants, choosing analytical priorities is challenging. The modern test methods are based on LC-MSMS, occasionally along with GC-MSMS, to lower the quantitative uncertainty, isotopic internal standards used wherever possible in LC-MSMS techniques.

3.1 Development of analytical methods: The two basic categories of analytical procedures are Classical methods and Instrumental methods. A "classical method" is a technique where the signal is inversely proportional to the absolute concentration of the analyte. When the signal is proportionate to the analyte concentration, the method is considered instrumental. The three basic categories of classical approaches are: Analyte separation, qualitative analysis, and quantitative analysis are the first three steps.

3.2 The need for method development: During this developing a drug and using manufacturing techniques, the main goal of analytical strategies is to gather information about efficacy, impurity, bioavailability, stability, and effect of producing parameters to confirm that, before the event of the newest technology.

3.3 The following are the stages that go into method developing:

(1) Analyte and standard characteristics: gathered all the information needed on the analyte and its structure, including its physical and chemical characteristics like solubility and optical isomerism.

(2) Technique requirements: Linearity, selectivity, specificity, range, accuracy, precision, LOD, LOQ, and other must be described to construct the analytical figures of advantage.

(3) System Appropriateness: The following criteria were used in the system suitability tests (SST) report: Efficiency (N), Capacity factor (K), Separation (Rs), Resolution (Rs), Tailing factor (T), and Relative variance are examples of theoretical plates (RSD)⁹.

4 Validation: Validation is based on regulatory specifications, but is not officially supported by them, and is therefore best viewed as an essential component of current good manufacturing practise (cGMP). Validation should be taken in to account for completely new equipment procedure that have been modified to meet new requirements procedure where the final result test is an unreliable indicator of product quality Validation is important [10].

5 CHROMATOGRAPHY TECHNIQUE: A physicochemical technique for separating mixtures of substances is chromatography. Chromatography uses two phases, a stationary phase and a mobile phase to separate a mixture of substances into their constituent components.

Thin layer chromatography and Paper chromatography are used for the (i) Separation, identification of mixtures of drugs of chemical or biological origin, plant extracts, etc; and to detect the presence of foreign substances in drugs.

Gas chromatography are mainly used for (i) Purification of compound can be determined for drugs like clove oil, atropine, sulphate, stearic acid; (ii) Quality control and analysis of drug product like antibiotics, general anaesthetics, antivirals etc; (iii)To determine the level of metabolites in body fluids like blood plasma, serum and urine.

5.1 Ion-Exchange Chromatography: It is a process that allows the separation of ions and polar molecules based on their affinity to the ion exchanger. Cations and anions can be separated using this method. This is used for separation of inorganic ions, sugars, amino acids and proteins also for the purification of solution free from ionic impurities and for extraction of enzymes from tissues.

5.2 Gel-Filtration Chromatography: The fundamental idea behind this technique is to use materials containing dextran to segregate macromolecules according to how differently their molecules are sized.

5.3 Ultra-Performance Liquid Chromatography (UPLC): This sophisticated method of liquid chromatography improves in three key areas: speed, resolution, and sensitivity.

5.4 High-Performance Liquid Chromatography (HPLC): To separate the components of a mixture, HPLC uses a liquid mobile phase. These components are first made to dissolve in a solvent, after which they are compelled to flow through a chromatographic column under intense pressure. The mixture separates into its component parts in the Column. HPLC used for identifying the active constituents in dosage forms; evaluation of pharmaceutical product shelf- life.

5.5. Automated development in HPTLC: The fundamental technique of TLC can be improved with ways to automate the various procedures, increase the resolution attained, and enable more precise quantitative measurements, HPTLC has nowadays become a standard analytical technique.

5.6. Development of RP-HPLC: The measurement of ATP, ADP, AMP, NADP+, NAD+, NADPH, and NADH in human erythrocytes using a simple and quick approach. On a 5-m Supelcosil LC-18 column with UV detection, RP-HPLC is used to complete the analysis.

5.7. LC-MS Method: Sensitivity, selectivity, study speed and cost-effectiveness of LC/MS procedures applied in variety of pharmaceutically relevant substances. These analytical functions have continuously advanced, making instruments more user-friendly and trustworthy. Applications of LC-MS method in clinical samples: It is a method using liquid chromatography-tandem mass spectrometry (LC-MSMS) for routinely evaluating patient samples and for the detection of mescaline in human urine samples.

6. SPECTROSCOPY TECHNIQUE:

The changes in rotational, vibrational or electronic energies are measured by spectroscopy. This method was specifically used in pharmaceutical analysis to analyse the dose forms in pharmaceutical businesses has steadily increased. Aspects of the colorimetric approaches include the following as well: (i) Reaction to complex creation; (ii) A catalysing outcome; (iii) Oxidation and reduction processes.

6.1 Ultraviolet-Visible Spectroscopy: It is based on the electromagnetic radiation's absorption in the UV/Vis area, with wavelengths between 200 and 400 nm (UV spectroscopy) and 400 and 800 nm (Visible spectroscopy).

6.2 Infrared (IR) Spectroscopy: It includes a variety of methods, many of which are based on absorption spectroscopy. Identification of functional groups is simple due to their absorption of characteristics.

6.3 Mass spectroscopy: It is a potent analytical technique that may be used to measure known materials, identify unidentified chemicals in a sample, and shed light on the structure and chemical characteristics of various molecules, the mass-to-charge ratio of ions is measured analytically via mass spectroscopy. Therefore, ions are separated on the basis of m/z values. Each positive ion formed directly or by fragmentation of the original molecule has a unique mass/charge ratio; this is useful for quantitative analysis of mixtures containing closely related compounds.

6.4 Nuclear Magnetic Resonance (NMR) Spectroscopy: Numerous nuclei have spin, and all nuclei are electrically charged, according to the NMR underlying principle. The most common types of NMR are proton and carbon-13 NMR spectroscopy, but it is applicable to any kind of sample that contains nuclei possessing spin.

6.5 Fourier-Transform Infrared Spectroscopy (FTIR): This technique helped scientists create a novel way by identifying the functional group and the original peak with relation to the compounds.

6.6 Phosphorimetry and Fluorimetry: These are analytical methods based on the absorption of electromagnetic radiation by the processed sample, which contains or produces molecules that absorb radiation in excited states; when the excited molecules return to the ground state; useful for the analysis of micro samples¹¹.

7. Pharmaceuticals' adverse effects on the environment: Toxicology and pharmacology don't seem to be as crucial to human health problems from drug exposure in the environment as environmental hygiene, for example:

(i) Endocrine-active drugs and hormones may prevent human sexual development because they interact with hormone systems and are highly active chemicals.

(ii) The toxicology and ecotoxicology fields are still grappling with the problem of medication administered through drinking water. Pregnant women, young children, and elderly persons may be at danger.

(iii) While diclofenac's effective concentration for chronic fish toxicity was in the range of wastewater concentrations, propranolol and fluoxetine had effective concentrations for zooplankton and benthic species that were close to the maximum recorded sewage treatment plant effluent concentrations.

(iv) By giving the oriental white-backed vultures direct oral exposure to diclofenac residues and treated livestock remains, researchers were able to replicate diclofenac residues and renal illness in vultures in an experimental setting¹².

8. Challenges Education and training is lacking:

There is a dearth of education and training; many hospitals and healthcare facilities make the error of failing to instruct and train the whole nursing team on correct drug disposal techniques. Nursing staff needs to receive professional training on various medications and the proper container for disposal of unclear collecting containers. This relates to education, training, and a staff of nurses that is overworked^13,14.

9. CONCLUSION:

Analytical methods, like the Spectroscopy and Chromatography is now recognised as a very sensitive and efficient separation technique. Chromatography is regarded as a recent scientific breakthrough that has had the greatest impact. Although HPLC was once only used by analysts, it is now frequently used by researchers, chemists, biologists, industrial employees, and other labs for quality control and research. The main purposes of analytical method development are for identification, purification, and ultimately to quantification any chemicals or drug etc. Therefore, an analyst can greatly benefit from the key aspects in calculating pharmaceutical formulations, bulk medications and their by-products in the environment. The outcomes of the chromatographic and spectrometry techniques are showed how accurate, precise, specific, linear, dependable, sensitive, and quick this analytical technique. In order to ensure that quality work is done in the process that supports the creation of medicines and products, validation is a vital approach in the pharmaceutical industry.

10. REFERENCES:

1. Carmen LC, Mariana L, Alina ME. Pharmaceutical residues in the environment - New European Integrated Programs Required. Revista De Chimie, 2016; 67 (5); 1008-1013.

2. Pietro Bruni. Impact of Pharmaceutical Pollution on Communities and Environment in India, Published in February 2016; 1-71.

3. Larsson DGJ. Release of active pharmaceutical ingredients from manufacturing sites: need for new management strategies. Integration Environment Assessment Management. 2010; 6: 184-186 (doi:10.1002/ieam.20).

4. Holm JV, Ruegge K, Bjerg PL, Christensen TH. Occurrence and distribution of pharmaceutical organic compounds in the groundwater downgradient of a landfill (Grindsted, Denmark). Environment Science Technology. 1995; 29: 1415-1420 (doi:10.1021/es0005a039).

5. Grabicova K, Grabic R, Blaha M, Kumar V, Cerveny D, Fedorova G, Randak T. Presence of pharmaceuticals in benthic fauna living in a small stream affected by effluent from a municipal sewage treatment plant. Water Research. 2015; 72:145-153.

6. Daughton CG, Ruhoy IS. Environmental foot print of pharmaceuticals thesignificance of factors beyond direct excretion to sewers. Environmental Toxicology and Chemistry. 2009; 28(12): 2495-2521.

7. Richardson ML, Bowron JM. The fate of pharmaceutical chemicals in the aquatic environment. Journal of Pharmacy and Pharmacology. 1985; 37(1):1-12.

8. Sherer JT. Pharmaceuticals in the environment. American Journal of Health-System Pharmacy. 2006; 63(2): 174-178.

9. Ravisankar P, Navya CN, Pravallika D, Sri DN. A review of step-by-step analytical method validation. IOSR JPharm. 2015; 5: 7-19.

10. Mahar P, Verma A. Pharmaceutical process validation: anover view. Int J Pharm Res Bioscience. 2014; 3: 243-262.

11. Masoom RS, Zeid A. AlO th man, Naﬁsur R. Analytical techniques in pharmaceutical analysis: Areview. Arabian Journal of Chemistry. 2017; 10: S1409-S1421.

12. Myranda E. Pharmaceutical Waste Disposal Challenges Facing Pharmaceutical Waste Management in Healthcare. July 22, 2020.

13. Syed ZR, Ahmad ZF. Diclofenac Sensitivity to Vultures’ Death and Environmental. International Journal of Human and Health Sciences. 2019; 4(1): 19-25. Doi: http://dx.doi.org/10.31344/ijhhs.v4i1.115.

14. ICH guideline Q2(R2) on Validation of Analytical Procedures, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Pharmaceuticals for Human use, Validation of Analytical Procedures Q2(R2) Draft version Endorsed on 24 March 2022.

Received on 22.11.2023 Modified on 19.03.2024

Asian J. Pharm. Ana. 2024; 14(3):201-204.

DOI: 10.52711/2231-5675.2024.00036