Annals of Phytomedicine 12(2): 299-303, 2023

DOI: [Link]
Annals of Phytomedicine: An International Journal 299
[Link]
Print ISSN : 2278-9839 Online ISSN : 2393-9885

Review Article : Open Access

An overview of analytical methods for quantification of paracetamol

R. Gandhimathi , V. Nivathra, and C. M. R. Kajhareshevarmaa
Department of Pharmaceutical Chemistry and Analysis, School of Pharmaceutical Sciences, Vels Institute of Science, Technology, and Advanced
Studies (VISTAS), Pallavaram-600117, Chennai, Tamil Nadu, India

Article Info Abstract

Ar tic le histo ry Both the international names paracetamol (used in Europe) and acetaminophen (used in the United
Received 13 November 2023 States) are official names in the case of the same chemical substance. In an attempt to exterminate worms
Revised 24 December 2023 in the 1880s, two teenage physicians acetanilide was administered to a patient at the University of
Accepted 25 December 2023 Strasburg accidentally in place of naphthalene. They observed that even though the drug greatly lowered
Published Online 30 December 2023 high fever, it possessed very little impact on intestinal parasites. After a year, Frederick Stearns and Co.,
a division of Sterling Drug Inc., started offering 500 mg of aspirin pills over the counter in Great Britain
Ke ywor ds under the brand name panadol. A spectrophotometric approach based on continuous flow for detecting
Acetaminophen paracetamol in pharmaceuticals is described. Created a stability-indicating technique to use the TLC
Prostaglandin densitometry method to figure out how much paracetamol is in pharmaceutical preparations. An effective
Acetanilide
approach for detecting acetaminophen in pharmaceutical formulations using reverse-phase high-
Spectrophotometric
Flow rate performance liquid chromatography was developed. At a flow rate of 1.78 ml/min, a combination of
methanol and water (1:2 v/v) is employed with a C18 stationary phase, with spectrophotometric detection
193.3 nm. Created a method for determining paracetamol using differential pulse voltammetry at a
carbon ionic liquid electrode. A carbon paste electrode (CPE) and carbon ionic liquid electrode (CILE) were
both used to study how paracetamol behaves electrochemically in a 0.1 m acetate buffer solution (pH
4.6). For example, long-term alcohol abuse combined with concurrent usage of medications that cause
enzyme induction, including barbiturates, or carbamazepine, could make paracetamol poisoning more
likely.

1. Introduction which were previously produced in 1878 by Harmon Northrop

Morse (Subhamalar et al., 2023).
Both the terms paracetamol (an international name used in Europe)
and acetaminophen (an international name used in the United States) Joseph von Mering, a pharmacologist from Germany conducted
are interchangeable official names for the identical chemical, which is two acetanilide derivatives’ initial clinical trials. Based on the data, it
taken from its chemical name: N-acetyl-para-aminophenol. This was incorrectly concluded that paracetamol had considerable toxicity,
drug has a long history of use and was discovered by chance, as much like acetanilide. As a result, phenacetin was the first derivative
important discoveries frequently do (Sumithra, 2023). to be used in medicine, in 1887. Before its long-term use was linked
In an attempt to exterminate worms in the 1880s, two youthful to nephritis caused by analgesics developing, phenacetin was a
physicians acetanilide was administered to a patient at the University common ingredient in analgesic combinations (Vimal Raj and Sumithra,
of Strasburg accidentally instead of naphthalene. They observed 2023). Paracetamol/acetaminophen gained popularity in 1948, six
that even though the drug greatly lowered high fever, it possessed months later after research by Brodie Bernard and Axelrod Julius
very minimal impact on parasitic intestinal worms. Following the showed another metabolite, phenylhydroxylamine, was what caused
prompt publication of their findings by two young physicians, methemoglobinemia and paracetamol served as the primary analgesic
Arnold Chan and Paul Heppa, acetanilide was first used in medicine and antipyretic properties of acetanilide and phenacetin’s active
in 1886, by the trade appellation antifebrin. It shortly became clear metabolite.
that despite its low cost of production, it was not possible to use
acetanilide because of its antipyretic properties, the majority In 1955, the laboratories of Mcneil brought paracetamol to the
concerning among which methemoglobinemia was one. That led to pharmaceutical sector as a pediatric prescription marketed as Tylenol
extensive research on less poisonous acetanilide derivatives. The children’s elixir, an analgesic and antipyretic (the Tylenol comes
most pleasing chemicals were phenol and N-acetyl-p-aminophenol, from N-acetyl-p-aminophenol), the chemical name for it. After a
year, the company Frederick Stearns and Co., a division of Sterling
Drug Inc., started offering 500 mg of aspirin pills over the counter in
Corresponding author: Dr. R Gandhimathi Great Britain under the brand name Panadol. Since its introduction
Professor, Department of Pharmaceutical Chemistry and Analysis, into the Polish market in 1961, paracetamol has been one of the most
School of Pharmaceutical Sciences, Vels Institute of Science, Technology popular and widely prescribed pain reliever drugs. The trade offer
and Advanced Studies (VISTAS), Pallavaram, Chennai-600117, Tamil
includes over 100 products that either contain paracetamol exclusively
Nadu, India
E-mail: dr gmathipharm2 01 7@g mail.c om
or in conjunction with additional active ingredients (Raghavi et al.,
Tel.: +91-9080766247 2023).
Copyright © 2023 Ukaaz Publications. All rights reserved.
Email: ukaaz@[Link]; Website: [Link]
300

levels can be used to categorize them as extensive, ultra-rapid, or

poor metabolizers (Alloui et al., 2002).
3.3 Drug interaction
Co-administration of several medications should be done with caution
as there may be interactions with them. For example, long-term
alcohol abuse combined with concurrent usage of medications that
cause enzyme induction, including barbiturates, or carbamazepine,
Figure 1: Structure of paracetamol.
may increase the likelihood of paracetamol production of NAPQI
2. Dose and toxicity. However, the exact mechanism is unknown due to
isoniazid’s status as an enzyme inhibitor (Amino Shariae and Khan,
The process of paracetamol oxidation, which primarily involves the 2015).
CYP2E1 enzyme, is minimal in newborns due to CYP2E1 action
rises with age, reaching adult levels between the ages of 1 and 10 3.4 Toxicity
years (Beauchamp et al., 2013). In contrast, adults’ livers mostly While acute overdose of paracetamol is generally safe, it can harm
metabolize paracetamol through 50-60% glucuronidation, 25-30% the kidneys, brain, and liver, even leading to death. On rare occasions,
sulfation, and less than 10% oxidation (Lee et al., 2016). even after a therapeutic amount, it causes these effects due to the
3. Pharmacology and recent findings and future directions presence of subclinical risk factors like glutathione deficiency or
“fast-metabolizer” status.
3.1 Mechanism of action
Nevertheless, use within the therapeutic range, especially frequent
Even though the exact manner in which the actions of paracetamol and consistent use, can also have less well-known effects on other
have not been completely elucidated, it is routinely given in addition organ systems (Ghanem et al., 2016).
to nonsteroidal anti-inflammatory drugs because of its ability to
block the pathways of cyclooxygenase (COX). Well, it is permissible 3.5 Recent findings and future directions
to use central conduct, which will gradually lead to a decrease in the Abdel Shaheed recently analyzed 36 publications’ worth of data and
symptoms of discomfort. A single theory is that paracetamol found that while paracetamol was ineffective in other conditions, it
increases the threshold for discomfort by suppressing prostaglandin did produce minimal alleviation of pain in tension, headaches, arthritis
production is mediated by two cyclooxygenase isoforms, COX-1 of the hips and knees, as well as pain following a craniotomy. The
and COX-2 . Among prostaglandins, the molecules that cause authors concluded that large-scale, superior trials are necessary to
discomfort sensations. Paracetamol has no effect on cyclooxygenase lessen ambiguity regarding the effectiveness of paracetamol in typical
in supplementary and hence possesses no anti-inflammatory pain syndromes (Bannwarth et al., 1992). Recent research has shown
qualities. Although, acetyl-salicylic acid (aspirin) is an unchangeable that acetaminophen can be safely utilized in those who have chronic
asset of COX and effectively prevents its action point, research has kidney illness, that it is significantly effective for pain following
revealed paracetamol inhibits COX laterally. According to research, arthroplasty, that ibuprofen works better than it does for discomfort
paracetamol effectively inhibits an alternative type of the enzyme, following laminectomy, that acetaminophen in emergency room saves
which differs from the recognized COX-1 and COX-2 variations. opioids, that paracetamol is not advised for pain following lumbar
This enzyme is referred to as COX-3. The temperature-regulating spinal stenosis with neurogenic claudication, and that paracetamol is
activity of acetaminophen is most probably due to focus efforts on recommended for pain following postcesarean sections and for
temperature regulation centers within the brain, which results in migraine (Sridhar Narayan et al., 2009).
supplemental vasodilation, perspiring, and heat dissipation. The
exact medium action of this medicine is not completely recognized at Experts should closely evaluate RCTs and other data before
this point, but unborn exploration might lead to a greater understanding implementing the findings in routine clinical practice, or rejecting
(Andersson et al., 2011). them. Therapeutic recommendations bridge the knowledge interval
between science and practical utilization in medicine. Because they
3.2 Pharmacokinetics
are derived from the consolidated medical data and take into account
Along with peak plasma concentrations occurring between 30 to 60 various financial, factors related to epidemiology, study, and treatment
min of administration and a plasma t1/2 of around 120 min, oral like the accessibility of substitute medical interventions, for instance-
paracetamol has high absorption. It diffuses throughout the majority they have the advantage of being more thorough. Practice guidelines
of bodily fluids and binds to plasma proteins less than NSAIDs. are, in our opinion, crucial instruments for controlling the intricacy
Glucuronide conjugates are eliminated via the kidneys. When taking of decision-making procedures (Blyth et al., 2019).
a therapeutic dose, 90-100% of the medication is perhaps found in 4. Analytical methods for paracetamol
the urine after the initial day. In the main process that converts
paracetamol into inert molecules by pairing with glucuronide and 4.1 Spectroscopic techniques
sulfate, a small amount is also turned oxidized by an enzyme system
A spectrophotometric determination of paracetamol was developed
called cytochrome P450, which includes the isoenzymes CYP2E1
using iodyl benzene. The spectrophotometric measurement of
and CYP1A2 . N-acetyl-p-benzoquinone imine is an alkylating
paracetamol (N- acetyl-4-aminophenol) was performed by oxidizing
metabolite, or paracetamol produces NAPQI when it is converted
it in acetone with iodyl benzene to get N-acetyl-1, 4-benzoquino-
through the enzymes CYP2E1 and CYP1A2 , and it may be this
neimine, a yellow-orange compound, which acquires highest possible
metabolite that causes liver damage. A person’s CYP2D6 expression
 301

color strength in a 1 min and peaks in absorption at 430 nm. 1.58103 in 4 ml sulfuric acid. It had a consistent color of bluish-violet. The
l/mol/cm is the highest molar absorption coefficient (Krishna Verma colored chemical has a maximum of around 550 nm. The Beer’s law
et al., 1985). was followed in concentration ranges from 100 to 300 g/m in 1ml
HCl and 300 to 800 g/ml in 1M medium containing acetic acid and
Flow injection and spectrophotometry were used to determine the
detection limits of 0.03 g/ml in 1ml HCl and 0.05 g/ml in 1m acetic
concentration of paracetamol. The analyte is oxidized alongside
acid medium, in that order (Pavan Kumar et al., 2011).
potassium hexacyanoferrate and is reacted using phenol. Both
responses are conveyed in an aqueous ammoniacal solution at 80oC. Paracetamol spectrofluorometric determination in formulations of
The concentrations of paracetamol are measured in the 0.25-30 ppm pharmaceuticals was developed. An easy and considerate way to
range (Martinez Calatayud et al., 1986). determine paracetamol has been described, which is based on the
paracetamol and cerium oxidation reaction. The species that glows is
A spectrophotometric approach based on continuous flow is a cerium reduction item with stimulation as well as release
described for identifying medicines that contain paracetamol. wavelengths respectively, 255 and 348 nm. Fluorescence over the
Reducing paracetamol examples are consistently hydrolyzed in a system, the intensity is linear. Paracetamol concentration has a
medium with alkali p-aminophenol that interacts using 3.5 m NaoH detection range of 150-750 g/l with a relative standard deviation
and o-cresol using a home microwave oven. The resultant blue (RSD) of 1.22% and 20 g/l, respectively (Hossein and Hamid, 2011).
derivative exhibits a maximum absorbance of around 620 nm. The
threshold for detection of the approach is 0.2 g/ml, the apparatus 4.2 Chromatographic techniques
follows from 0.6 to 20 g/ml, and Beer’s law applies (Andres Criado A high performance liquid chromatography in reverse phase method
et al., 2000). was created for identifying pharmaceutical formulations containing
The fast technique using spectrophotometry is created to determine acetaminophen. The stationary phase of C18 is employed with a
acetaminophen. It is predicated upon a 15 min oxidation in 6 m 80°C combination of methanol and water (1:2 v/v) flowing at 1.78 ml/min
sulphuric acid and detection around 580 nm (Salah M. Sultan , 1987). and at 193.3 nm of spectrophotometric detection. The internal
standard sulphamethoxazole and the analysis take about 5 min (Sinan
The indirect determination of paracetamol, the luminol-H2O 2- Fe suzen et al., 1998; Sujatha Samala et al., 2022).
(CN) 63 system was developed. The method operates by oxidizing
paracetamol with hexacyanoferrate (III) and then blocking the A high-performance liquid chromatography approach measuring
luminol-hydrogen peroxide reaction. The method yielded a linear pharmaceutical formulations of the quantity of acetaminophen was
created. This only takes a few minutes and has sharp peaks that are
calibration curve with a range of 2.5 to 12.5 g/ml (Gregorio alapont et
noted. 20 cm x 4.6 mm of the column in stainless steel loaded with
al., 1999).
ocadesence and glued to permeable silica. It employs 10 mm and 0.2
An approach using spectrophotometry to measure tablets and pure ml per min through a 20-micrometre loop injector with a spectrum
paracetamol was developed. The strategy is predicated on the drug photometer set to 272 nm. The retention periods for 4-ammino
interacting with the molybdate of ammonium in a very acidulous phenol and sample solution are 4.388 and 4.542, respectively
solution to create molybdenum blue. Beer’s law was obeyed by (Narwade, 2014; Jahnavi Bandla and Ashok Gorja, 2022).
paracetamol concentrations as high as 6 g/ml, and 0.10 g/ml was the
A technique was created for determining the quantity of paracetamol
detection limit (p = 0.05). At 670 nm, the molar absorptivity was 2.6
in pharmaceutical preparations using the TLC densitometric
x 104 1/mol/cm, and the reaction’s Sandell’s sensitivity in this regard
approach. The drug is dissolved in methanol and then spotted onto
was 0.0059 gcm2 each absorbance unit of 0.001 (Basilio Morelli, a small amount of silica gel G254 using this procedure. On silica gel,
1989). paracetamol was separated using a mobile phase of ethyl
A sophisticated technique was created for determining acetaminophen acetate:benzene: acetic acid at an equation of 1:1:0.05 v/v/v. The
in medicines using direct FTIR spectroscopy. The process involves absorption (or reflectance) of the divided medication was measured
dissolving paracetamol in a 10% v/v ethanol solution in CH2Cl2 and at a wavelength of 250 nm. Curves of calibration for paracetamol are
measuring absorbance directly at 1515 cm -1, with measurement created in the 5-20 mcg/spot concentration range. Quantification is
correction using the 1900 cm-1 baseline that was set. A method can be possible by doing a comparison between the areas under the peaks
carried out in the flow injection as well as the stopped-flow modes, discovered while scanning the thin-layer chromatographic plates in a
with a sensitivity of roughly 0.09 A ml/mg in both cases and a spectral densitometer. An approach was utilized in formulations of
threshold for detection of 8 g/ml in the mode of stopped-flow and 33 pharmaceuticals, and the findings were compared statistically to the
g/ml in the mode of flow injection (Zouhair Bouhsain et al., 1996). results acquired using the mode of reference (Nadia and Mostafa,
2010; Mohammed Zafar et al., 2020).
A device that gauges the transmission of whole tablets between 600
and 1900 nm in wavelength, spectra was captured. Using two A unique method for determining the kinetics was suggested for
multivariate calibration techniques, spectral data were analyzed, paracetamol in pharmaceuticals. The process is based on tracking
namely stepwise multiple linear regression (SMLR) and partial least concentration changes in a matrix reaction system using
squares regression (PLSR) (Eustaquio. et al., 1999). potentiometric monitoring that is close to the bifurcation point and
in a stationary condition that is stable and not in equilibrium. In the
A straightforward and precise technique was created for determining matrix system, the bray-liebhafsky oscillatory reaction is employed
the presence of acetaminophen in the formulations of situation under study. A Pt electrode measures the matrix system in
pharmaceuticals. In the presence of 1ml HCl and 1ml acetic acid, response to disturbances generated by varied paracetamol focal points.
10.0 mg of sodium bismuthate was added after dissolving paracetamol The proposed method is based on a linear relationship between the
302

logarithms of the increased amounts of paracetamol and the maximum (VISTAS), Pallavaram, Chennai, for providing all necessary facilities
potential shift, Em. It is produced under optimal experimental for the completion of this review study.
conditions for paracetamol doses ranging from 0.0085 to 1.5 mol.
The suggested method’s sensitivity and precision were excellent, Conflict of interest
with a detection limit of 0.0027 mol and 2.4% of R.S.D (Natasa The authors declare no conflicts of interest relevant to this article.
Pejic et al., 2006).
Reference
A distinct pulse voltammetry was used on a carbon ionic liquid
Alloui, A.; Chassaing, C.; Schmidt, J.; Ardid, D.; Dubray, C. and Cloarec, A. (2002).
electrode to develop a method for determining paracetamol. A
Paracetamol exerts a spinal, tropisetron-reversible, antinociceptive
conventional carbon paste electrode (TCPE) and a carbon ionic liquid effect in an inflammatory pain model in rats. Eur. J. Pharmacol.,
electrode (CILE) were used to study the electrochemical behavior of 443 :71-77.
paracetamol in 0.1 m acetate buffer solution (pH 4.6). The CILE was
Amino Shariae, A. and Khan, A. (2015). Acetaminophen: Old drug new issues.
constructed by substituting conductive hydrophobic room
J. Endod., 41 :588-593.
temperature ionic liquid, 1-butyl-3-methylimidazolium hexafluoro-
phosphate, for nonconductive organic binders. According to findings, Andersson, D. A.; Gentry, C.; Alenmyr, L.; Killander, D.; Lewis, S. E. and Andersson,
A. (2011). TRPA1 mediates spinal antinociception induced by
the (CILE) displayed a greater ability to reverse based on the redox
acetaminophen and the cannabinoid - tetrahydrocannabinol. Nat.
of paracetamol using electrochemistry. When the approach was Commun., 2: 79-87.
employed to detect the presence of paracetamol, the average recovery
Andres Criado; Soledad Cardenas; Mercedes Gallego and Miguel Valacarcel
was 99.3% in urine samples and 98.5 % in tablet samples (Shang (2000). Continuous flow spectrophotometric determination of
Guan. et al., 2008). paracetamol in pharmaceuticals following continuous microwave-
assisted alkaline hydrolysis. Talenta., 53 (2):417-423.
A method for determining the amount of API in paracetamol tablets
using cyclic voltammetry was created and a glassy carbon electrode Bannwarth, B.; Netter, P.; Lapicque, F.; Gillet, P.; Pere, P. and Boccard, E. (1992).
was used to detect the acetaminophen peak current in a pH 7.0 0.10 Plasma and cerebrospinal fluid concentrations of paracetamol after
a single intravenous dose of propacetamol. Br. J. Clin. Pharmacol.,
mol/l phosphate buffer. The best 0.0005 v was discovered to be the
34: 79-81.
step potential and 0.1000 v/s to be the scan rate. Between 3 and 240
g/ml was the linear calibration range. With a 3.0 g/m as the detection Basilio Morelli (1989) Spectrophotometric determination of paracetamol
threshold and recovery rate of 99.1% (Kanita Tungkananuruk et al., in pure form and in tablet. J. Pharm and Bio. Anal., 7(5):577-584.
2005). Beauchamp, G.A.; Hart, K.W.; Lindsell, C.J.; Lyons, M.S.; Otten, E.J.; Smith, C.L.;
Ward, M.J. and Wright, S.W. (2013). Performance of a multi-disciplinary
5. Conclusion emergency department observation protocol for acetaminophen
overdose. J. Med. Toxicol., 9 (3):235-241.
In conclusion, the development of analytical methods by HPLC for
paracetamol/acetaminophen in the form of soft gelatin capsules. These Blyth, F.M.; Briggs, A.M.; Schneider, C.H.; Hoy, D.G.; March, L.M (2019). The global
tools can be used to assess this combination regularly in future burden of musculoskeletal pain. Am. J . Public Health., 109 :35-40.
advancements. This method is shown in this review for developing Dhritimoni Devi.; and Sumithra, M. (2023). Development and validation of
the analytical method of paracetamol in the HPLC technique. The analytical technique for the evaluation of insulin glargine by RP-
detection and quantification limits of acetaminophen were determined HPLC. Ann. Phytomed., 12 (1):611-615.
to be 120 ng/ml and 360 ng/ml, respectively. The recovery and assay Eustaquio, A.; Blanco, M.; Jee, R.D. and Moffat, A.C (1999). Determination of
investigations of paracetamol were from 99 to 102%, it is clear that paracetamol in intact tablets by use of near-infrared transmittance
the proposed approach applies to the analysis of paracetamol quality spectroscopy. Analytica Chimica Acta., 383 (3):283-290.
control. Ghanem, C.I.; Perez, M.J.; Manautou, J.E. and Mottino, A.D. (2016).
Acetaminophen from liver to brain: New insights into drug
The development of innovative technologies for detecting and
pharmacological action and toxicity. Pharmacol Res. Jul., 109 :119-
quantifying paracetamol in medicines, and environmental matrices is 31 .
critical for avoiding and controlling its potentially harmful
Gregorio Alapont, A.; Lahuerta Zamora, L. and Martinez Calatayud, J. (1999).
consequences. Given the possibility of paracetamol buildup efficient,
Indirect determination of paracetamol in pharmaceutical
delicate, and straightforward analytical techniques in surface water, formulations by inhibition of the system luminol–H 2 O 2–Fe3 (CN) 6 -
drinking water, and wastewater is critical for detection. The HPLC chemiluminescence. J. Pharm. and Biomed. Analysis, 21 (2):311-
analytical method has proven to be reliable for quality control of 31 7.
paracetamol/acetaminophen formulations with complicated
Hossein Tavallali and Yahya Hamid (2011). Spectroflu orometric
compositions and may be used in standard analytical laboratories determination of Paracetamol in pharmaceutical formulations.
without the need for expensive instrumentation. As a result, the Asian J. pharm Res. Dev., 2 (1):11-17.
approach can be utilized for routine raw material analysis as well as
Jahnavi Bandla and Ashok Gorja (2022). Development and validation of
in vitro dissolution studies of dose formulations including
sample simultaneous analysis for ertugliflozin and metformin by
paracetamol. reverse phase-high performance liquid chromatography (RP-HPLC)
Acknowledgments in tablet dosage form. Ann. Phytomed., 11 (1):83-90.
Kanita Tungkananuruk; Nipon Tungkananuruk and Duncan Thorburn Burns
The authors would like to express their gratitude to the management (2005). Cyclic voltammetric determination of acetaminophen in
of Vels Institute of Science, Technology, and Advanced Studies paracetamol tablets. KMITL Sci. Tech. J., 5 (3):160-164.
 303

K rishna, K.; Verma andArchana Jain (1985). Spectrophoto-metric Salah Sultan, M. (1987). Spectrophotometric determination of paracetamol
determination of paracetamol with iodobenzene. Talanta., in drug formulation by oxidation with potassium dichromate.
32 (3):238-240. Talanta., 34 (7):605-608.
Lee, S.K. Quinonez, R.B. Chuang, A. Munz, S.M. Dabiri, D. (2016). The case for Shang Guan, X.; Zhang, H. and Zheng, J. (2008). Electrochemical behavior and
improved interprofessional care: Fatal analgesic overdose secondary differential pulse voltammetric determination of paracetamol at a
to acute dental pain during pregnancy. Case Rep. Dent., 16 :746- carbon ionic liquid electrode. Anal. Bioanal. Chem., 391 (3):1049-
76 2. 55 .
Martinez Calatayud, J.; Pascual Marti, M.C. and Sagrado Vives, S. (1986).
Sinan Suzen.; Cemal Akay.; Aenol Tartilmis.; R. Serdar Erdol.; Atilla Onal and
Determination of paracetamol by a flow injection-spectrophoto-
Aemsettincevheroglu. (1998). Quantitative of acetaminophen in
metric method. Analytical Letters, 19 :19-20.
pharmaceutical formulation using HPLC. Fac. J, Pharm., 27 (2):
Mohammed Zafar; Mohammed Abdul Rasheed Naikodi; Kommu Nagaiah and 93-1 00.
Sunder Raju, P.V. (2020). Development of standard operating
procedures and quality standards of kushta gaodanti with HPTLC Sridhar Narayan; Pradeep Kumar; Rakesh K Sindhu; Ayushman Tiwari and Manik
fingerprinting and hyphenated techniques. Ann. Phytomed., 9 (1): Ghosh (2009). Simultaneous analysis of paracetamol and tramadol -
66-77. analytical method development and validation. Der. Pharma.
Chemica., 1 (2):72-78.
Narwade, S. S. (2014). Qualitative and quantitative analysis of paracetamol
in different drug samples by HPLC technique. J. Appl Chem., 7(8):46- Sujatha Samala; Palatheeya Sujatha and Tharun. G. (2022). Method
49 . development and validation of bendamustine HCl injection by using
RP-HPLC. Ann. Phytomed., 1 :95-100.
Nadia, M. and Mostafa (2010). Stability indicating method for the
determination of paracetamol in its pharmaceutical preparations by Subhamalar, K.; Vijey Aanandhi, M. and Afroz Patan (2023). Analytical method
TLC densitometric method. J. Saudi Chem. Soc., 14 (4):341-344. development and validation of rifaximin and ornidazole in bulk
and combined tablet dosage form as per ICH guidelines. Ann.
Natasa Pejic.; Ljiljana Kolar-Anic and Slobodan Anic (2006). Determination
Phytomed., 12 (1):595-600.
of paracetamol in pure and pharmaceutical dosage forms by pulse
perturbation technique. J. Pharm. Biomed. Anal., 41 (2):610-615. Vimal Raj, M. and Sumithra, M. (2023). Analysis of second-generation
Pavan Kumar, G.V.S.R.; Bhuvan Kumar, G.; Chandra Sekhar, T.; Sreerama and antihistamine fexofenadine soft gelatin capsules and its related
Murthy, B.(2011). Spectrophotometric determination of paracetamol compound by using RP-HPLC. Ann. Phytomedicine., 12 (1):616-
using sodium bismuthate as chromogen, IJRCE., 2 (1):231-235. 62 7.

Raghavi. R.; Vijey Aanandhi, M. and Sumithra, M. (2023). Analysis of Zouhair Bouhsain; Salvador Garrigues and Miguel de la Guardia (1996). Flow
phytoconstituents and its phytoformulation of curcumin chewable injection-Fourier transform infrared spectrometric determination
tablet as per ICH guidelines, Ann. Phytomed., 12 (1):601-605. of paracetamol in pharmaceuticals. Analyst., 121 :635-639.

Citation R. Gandhimathi, V. Nivathra, and C. M. R. Kajhareshevarmaa (2023). An overview of analytical methods for
quantification of paracetamol. Ann. Phytomed., 12(2):299-303. [Link]