^1-7Department of Pharmaceutical Analysis and Quality Assurance, DKSS`s Institute of
Pharmaceutical Science and Research (For Girls),Swami-Chincholi, Bhigwan ,
(Affiliated to Dr.Babasaheb Ambedkar Technological University, Lonere,Pune),Maharashtra, India.

⁸Department of Pharmacology, Dattakala College of Pharmacy, Bhigwan,
(Affiliated to Savitribai Phule Pune University, Pune), Maharashtra, India.

Corresponding  author email: chinababu.rao@gmail.com 

Article Publishing History

INTRODUCTION

Paracetamol (figure-1) is an analgesic and antipyretic [1]. Numerous spectrophotometric techniques have been documented for determining paracetamol,formed the red dye with diazotized 4-nitroaniline (DNAN) in sodium carbonate medium¹, majority of published methods were on hydrolysis of the compounds leading to the Schiff base formed with a substituted benzaldehyde², reaction of sodium nitrite with drug forms the diazonium salt and coupling reagent was 1-Napthol³, 2,4,6-trimethoxybenzaldehyde coupling formed pink colour², the drug forms the colour with p-dimethyl amino benzaldehyde in the  95% ethanol and 2M HCl⁵, estimation of drug in plasma with sodium nitrite, one of the most often used Cl reagents is luminol [6]. Several oxidizing chemicals, including permanganate (MnO₄^-2), oxidize it, hydrogen peroxide (H₂O₂), periodate (IO₄^-2), and hypochlorite (ClO^–).

Luminol undergoes oxidation to yield 3-aminophthalate, an excited state product that emits blue light with a maximum wavelength of 425 nm. Additionally, diperiodatocuprate (III) (DPC), diperidoatonicklate (IV) (DPN), and diperidodatoargentate (III) (DPA)are among the other high and unusual oxidation state transition metal complexes that are being used more and more for analytical purposes⁷. Microwave assisted hydrolysis of paracetamol with 2,2-(1,4-phenylenedivinylene) bis-8-hydroxyquinoline⁸, the colorimetric reagents Fe⁺³ and K₃[Fe(CN)₆] were employed for the determination of compound with exhaled breath condensate technique (EBC),  Fe⁺³ reduced to Fe⁺² and K₃[Fe(CN)₆] chelated the Fe^{+2 9} , oxidative coupling reaction of para amino phenol with p-xylenol (2,5-diethylphenol)¹⁰, reduce the compound with cerric ammonium sulphate¹¹, the process produces a prussian blue (PB) complex by oxidizing paracetamol with Fe(III) and then reacting with ferricyanide in the presence of HCl¹² , charge transfer complex formed between chromogenic reagent of  chlorferone with drug¹³, oxidative coupling reaction of paracetamol with phenylephrene hydrochloride in ambient oxygen and in an alkaline media, produce a stable, water-soluble indophenol dye¹⁴, coupled reaction of 1-napthol¹⁵, indirect determination of paracetamol with Luminol-H₂O₂-Fe(CN)^(-3)₆¹⁷ and based on the oxidation between drug and Fe(CN)^(-3)_6, it prevents reaction between luminol and hydrogen peroxide [18].

The analyte oxidised with K₃[Fe(CN)₆] at ambient temperature in ammonical aqueous solution by using anionic ion exchange column in the flow injection-spectrophotometric method^19,20, talkaline hydrolysis of the analyte formed blue indophenol dye with 8-quinolinol in presence of KIO₄^21-25, reaction with 2-nitroso-1-naphthol-4-sulfonic acid²⁶, Stable colour complex produced with a Folin-Ciocalteau reagent²⁷, formation of 2-nitro-5-acetamidophenol derivative with nitrous acid in an alkaline medium²⁸.intrusion of salicylates and salicylamide in the colorimetric nitration method and grieves the estimation of paracetamol²⁹,based on ring-nitration of the drug³⁰, using chlorferone³¹, using ZrO₂ (IV) and NH₄NO₃ (V)³² ,Colorimetric method of Glynn and Kendal ³³, reduction of tris(2,2′-bipyridyl) ruthenium(III)³⁴, luminol-permanganate based reaction³⁵, using N, N-dibromo dimethylhydantoin³⁶,  4-(Dimethylamino) benzaldehyde react with N-(4-hydroxyphenyl) ethanamide in 2M HCl after heating³⁷, luorophore heroin reagent was used with NaClO oxidizing agent and pH was optimized at 10 with borate buffer³⁸. NaClO oxidizes the analyte and excess of the oxidant determined with o-tolidine dichloride as chromogenic reagent at 430 nm ³⁹.Paracetamol was dissolved in 4M sulphuric acid and treated with 10.0 mg of sodium bismuthate in the presence of 1M HCl and 1M acetic Acid. It exhibited a stable bluish-violet colour⁴⁰.

Paracetamol to p-aminophenol that reacts with S2- in the presence of Fe³⁺ as oxidant to create a dye that resembles methylene blue and has an ʎmax at 540 nm⁴¹.The N-(4-hydroxyphenyl) ethanamide on the hydrolysis formed p-aminophenol and oxidant is dissolved oxygen in the alkaline medium, further formed in to N-acetyl-p-benzoquinone imine, which is capable to produce green indophenol dye with tiron⁴², estimate the drug by using cadmium pentacyanonitrosylferrate modified glassy carbon electrod⁴³, Fe⁺³ ions oxidize paracetamol and salicylamide when 1,10-phenantroline is present⁴⁴.

MATERIAL AND METHODS

The materials were used in the colorimetric methods paracetamol, diazitized 4-nitroaniline¹,HCl, benzaldehyde, Na₂CO₃, 2,4,6-trimethoxybenzaldehyde², resorcinol, ammonium sulfamate³, sodiumnitrite, 1-Naphthol^3,4,6, 4-amino phenol, Na₂SO₄, tetrahydroxycalix, indophenol dye⁴, dimethylamino benzaldehyde⁵, chloroacetic acid, NaOH, sulphamic acid,ethanol, luminol, KMnO₄, H₂O₂, KOH⁷, diperidodatoargentate (III)⁷, K₃[Fe(CN)₆], FeCl₃.6H₂O⁹, sodium periodate, tylenol¹⁰, ascarbic acid, phenylephrine hydrochloride, 2,6-dichloro indophenol, n-polopiryna¹¹, styrene, maleic anhydride, benzoyl peroxide, tetrahydro furan, diethyl ether, acetonitrile, poly (styrene-alt-maleic acid), methanol¹², 2,2-(1,4-phenylene divinylene) bis-8-hydroxyquinoline, ferric chloride, p-xylenol (2,5-diethylphenol), potassium ferricyanide^12,16, protryliptyline HCl, chlorferone^13,14,31, cerric amonium sulphate¹³, Iron (III)¹⁵, Zirconium (IV) oxide, ammonium trioxovanadate (V)³², N,N-Dibromo dimethylhydantoin³⁶, O-tolidine³⁹, Cadmium Pentacyanonitrosylferrate⁴³  

Preparation of  sample solutions: The majority of published methods were reported the preparation sample solutions  depends on acid hydrolysis of the paracetamol with substituted benzaldehyde forms the Schiff base², microwave assisted hydrolysis⁴, few methods have been reported on coupling reactions with coupling reagents², oxidation of the drug with oxidizing agents and oxidation state transition metal complexes and formation of charge transfer complexes⁷.

RESULTS AND DISCUSSION

The created procedures were validated in accordance with several recommendations, and the results produced fell within the acceptable range. The reported methods were shown good linearity and regression coefficient values were found to be greater than 0.999. The linearity range were found to be 0.5-20 µg/mL¹ for batch method 1-150 µg/mL for FI method¹, 20-100 µg/mL², 2-10 µg/mL³, 1.5-12 µg/mL for conventional UV method for cloud point extraction technique the linearity range reduced to 0.14 – 1.5 µg/mL⁴ (figure-2), 1-5 mg/mL⁵, 25-400 mg/L⁶, 0.075-0.75 mg/L⁷, 0.44-5.5 mg/L⁸, 0.2-10 µg/mL⁹, 25-600 µg/mL¹⁰, 0.01-0.5µg/mL¹², 40-160 µg/mL¹³, 50-500 mg/L²⁸, 0.5-24 µg/mL¹⁴, 2-10µg/mL¹⁵, 0.1- 2.4µg/mL¹⁶, 2-16 mg/mL¹⁷. The %RSD of the accuracy obtained results were found to be within the limits as per guidelines.

The concentration ranges of the reported methods were found to be from 0-60 mg/ml, 0.8 – 3.36 mL, 0 to 10 µg/ml, 0.01 – 0.70, 1.5—12 mg/mL, 0.075-0.75 mg/L, 0.2–10.0 μg/mL, 2.5-25 µg/mL and >70 µg/mL , 25 to 60 mg/ml,0.25-30 ppm¹⁹, 0.2-20 ppm²⁰,     f 0.01-0.5 mg/mL, 10.00–60.00 g/mL, 0.5-24 µg/mL, 2 – 10 μg/mL, 1.0-3.0 mL. The reported values were found the good LOD & the lowest LOD is 0.0369 µg/mL whereas the highest LOD is 40.0 mg/mL. The various methods have been reported and values were found to be 40.0 mg/mL, 0.0007 mg/mL, 0.2 µg/mL, 0.49 µg/mL, 0.007 µg/mL, 0.0578 µg/mL, 0.02 g/mL, 0.03 g/mL, 0.0448 mg/mL. The quantification limit values were found to be 0.002 mg/L, 0.166 mg/mL, 0.1753 g/mL, 0. 10 g/mL, 0.08 mg/mL, 0.149 mg/mL, 0.121mg/mL. The %RSD values of robustness were found to be within the limits as per guidelines.

The review article focused on the colourimetric determination of paracetamol with different colouring reagents and validation parameters. The Hayati filik et al⁴ reported lowest linearity concentration range from 0.14-1.5 µg/mL with CPE method by using with colourant calixarene (CAL4) in the presence of KIO₄ oxidant and colour of the solution was blue . Cloud point phase separation was done with Triton X-114 (surfactant micelles) by addition of Na₂SO_4. It is the high sensitive method because of detection limit was found to be 40ng/mL.⁴

Figure 2:  Absorption spectrum of the reaction product with and without Triton-X114⁴
 C_a=ʎmax-580nm ;   C_b= 590nm

Paracetamol estimated in urine by using different colouring reagents and their linearity
concentration values were reported in table 1.

Table 1. Colorimetric estimation of Paracetamol in Urine⁴

Method	Linearity range (µg/mL)	LOD (ng/mL)	Reference
Phenol	100-800	NR	Welch et al47
o-Cresol	0.3-12	100	Criado et al45
Xylenol	20-400	NR	Chen et al49
Resorcinol	2-100	900	Bocxlaer et al48
8-hydroxyquinoline	0-2.5	NR	Morris et al50
Derivative UV	5-30	2000	Parojicic et al51
Diazotisation	2-10	NR	Heirwegh et al46
ELSD	1-100	300	Criado et al52
UV-Visible	1.5-12	500	Hayati Filik  et al4
CPE-UV-Visible	0.14-1.5	40	Hayati Filik et al4

CONCLUSION

The paracetamol was estimated colorimetrically by using spectrophotometer with different coloring reagents. The charge transfer complex formed between chromogenic reagent of chlorferone with drug and shown sensitivity of the method. Different oxidation reactions were carried with oxidizing (coupling) agents were used with alkaline or acidic medium and produces the more intense colour, determined in visible range. The colourant calixarene (CAL4) in the presence of KIO₄ oxidant the drug was produced blue colour. This reagent used for the estimation of drug in the urine, with cloud point phase separation Triton X-114 (surfactant micelles) was used by addition of Na₂SO_4.

It is the high sensitive method because of LOD was found to be 40 ng/mL and linearity range was found to be 0.14-1.5 µg/mL. The drug produces the stable colored complex with Folin-Ciocalteau reagent it enhance the sensitivity and stability of the method. The other colorants were used  benzoyl peroxidepoly (styrene-alt-maleic acid), 2,2-(1,4-phenylene divinylene) bis-8-hydroxyquinoline, ferric chloride, P-xylenol (2,5-diethylphenol), potassium ferricyanide^12,16, protryliptyline HCl, chlorferone^13,14,31, cerric amonium sulphate¹³, Iron (III)¹⁵, Zirconium (IV) oxide, ammonium trioxovanadate (V)³², N,N-Dibromo dimethylhydantoin³⁶, O-tolidine³⁹, Cadmium Pentacyanonitrosylferrate⁴³.

Conflict of Interest: The authors have stated that they don’t have any conflicting interests.

ACKNOWLEDGEMENTS

The authors express gratitude to Dattakala Shikshna Santhan’s Management for providing requirements.

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