RESEARCH ARTICLE | MAY 09 2023

Qualitative and quantitative analysis of marketed cimetidine

tablet preparations by developed and validated
spectrophotometry ultraviolet 
Nerdy Nerdy  ; Linda Margata; Nilsya Febrika Zebua; ... et. al

AIP Conference Proceedings 2480, 040017 (2023)

https://doi.org/10.1063/5.0103638

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 Qualitative and Quantitative Analysis of Marketed
Cimetidine Tablet Preparations by Developed and Validated
Spectrophotometry Ultraviolet

Nerdy Nerdy1,a), Linda Margata1,b), Nilsya Febrika Zebua1,c), Puji Lestari2,d),

Firdaus Fahdi2,e), Tedy Kurniawan Bakri3,f)

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1)
Department of Pharmacy, Faculty of Pharmacy, Universitas Tjut Nyak Dhien, Sei Sikambing, Medan Helvetia,
Medan, Sumatera Utara, Indonesia, 20123
2)
Department of Pharmacy, Faculty of Pharmacy, Institut Kesehatan Deli Husada Deli Tua, Deli Tua Timur, Deli
Tua, Deli Serdang, Sumatera Utara, Indonesia, 20355
3)
Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Syiah Kuala, Kopelma
Darussalam, Syiah Kuala, Banda Aceh, Aceh, Indonesia, 23111

a)
Corresponding author : nerdy190690@gmail.com
b)
lindamargata@hotmail.com
c)
nilsya.zebua@gmail.com
d)
pujilestari87@gmail.com
e)
daus2966@gmail.com
f)
tedykbakri@unsyiah.ac.id

Abstract. The qualitative and quantitative analysis are critical parameters in quality control to ensure the efficacy, safety and
quality of a drug. Cimetidine is a drug that is widely used in the treatment of peptic ulcers. The molecular structure of cimetidine
has a chromophore group and an auxochrome group which allows for ultraviolet spectrophotometric analysis. The purpose of this
study is to develop, validate, and apply a simple and fast ultraviolet spectrophotometric method in qualitative and quantitative
analysis of cimetidine compounds in tablet preparations on the market, both preparations with generic names and preparations with
trade names. The solvents used were hydrochloric acid solution 0.1 N as acidic solvent and sodium hydroxide solution 0.1 N as
basic solvent. The results showed that qualitative and quantitative analysis of the cimetidine compound by ultraviolet
spectrophotometry both with acidic solvent and basic solvent can be applied for routine analysis and has good validity. The
qualitative and quantitative analysis of cimetidine tablet preparations in circulation were also successfully applied and met the
requirements of the cimetidine tablet monograph in Indonesian Pharmacopoeia, 6th edition, year 2020.
Keywords : Qualitative, Quantitative, Cimetidine, Development, Validation, Ultraviolet

The 4th International Conference on Science and Technology (ICST) 2021

AIP Conf. Proc. 2480, 040017-1–040017-9; https://doi.org/10.1063/5.0103638
Published by AIP Publishing. 978-0-7354-4463-8/$30.00

040017-1
 INTRODUCTION
Peptic ulcer is a lesion usually located in the stomach or proximal duodenum. It is induced by acid and indicated by
the damage of mucosa which extends into the submucosa or muscularis propria [1]. The prevalence of peptic ulcer
disease has been estimated to be 5–10% of the general population. However, epidemiological studies recently have
shown that there has been a sharp decrease in peptic ulcer incidence, rates of hospital admissions, and mortality [2].
This might be due to the introduction of new therapies and improved hygiene, which resulted in a decline in
Helicobacter pylori infections [3].
Cimetidine a H2-receptor antagonist, is a drug effective in managing gastric hypersecretion. Cimetidine has been used
in the management of reflux esophagitis disease and prevention of stress ulcers [4]. Cimetidine reduces gastric acid
by blocking histamine from stimulating the H2-receptors located on the gastric parietal cells (these cells are
responsible for hydrochloric acid secretion and secretion of the intrinsic factor [5]. Figure 1 show the molecular
structure of cimetidine.

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FIGURE 1. The molecular structure of cimetidine

Currently, quantitative analysis of pharmaceuticals containing cimetidine can be determined using high performance
liquid chromatography [6]. The use of ion pairing reagents like sodium hexasulfonate, although giving high resolution,
could cause a downside effect on column performance. Due to the strong hydrophobic interactions, ion pairing reagent
cannot be completely flushed from the column even after extensive washing [7]. In addition, high performance liquid
chromatography methods generally require sophisticated and expensive equipment, provision for use and disposal of
solvents, labor-intensive sample preparation procedure, and personal skills in chromatographic techniques [8].
Spectrophotometry method has some advantages compares to high performance liquid chromatography methods.
Spectrophotometry is more practical (less-time-consuming, simpler, and more convenient) and less expensive [9]. As
seen in Figure 1, cimetidine is a compound with an imidazole ring. The chromophore group in cimetidine molecular
structure enables it to be determined by spectrophotometry [10]. Therefore, the objective of this study is to develop
and validate an assay method for cimetidine tablets using UV-Vis spectrophotometry.

MATERIALS AND METHODS

TOOLS
Ultraviolet Visible Spectrophotometer (Agilent), Analytical Balance (Sartorius), Water Purifier (Merck), and
Glassware (Iwaki)
MATERIALS
Hydrochloric Acid (HCl) 37 % (Merck), Sodium Hydroxide (NaOH) Pellet (Merck), Purified Water (Merck),
Cimetidine (United States Pharmacopoeia).
Samples
Sampling was carried out purposively, that is, without comparing samples from one sampling location with samples
from another, because the sample was considered homogeneous. The samples used in this study are : Cimetidine
(Kimia Farma), Cimetidine (Bernofarm), Cimetidine (Ifars), Omekur ® (Mutiara Mukti Farma), Lexamet® (Molex
Ayus), Licimet® (Holi Pharma), Corsamet® (Corsa Industries), and Gastricon® (First Medifarma).

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 Method Development
The analytical method used in this research were based on the analytical method developed by Nerdy et al., 2017 with
slight modification. The steps for this research includes preparation of solvent, preparation of standard stock solution
and standard solution, preliminary analysis (determination of the wavelength that gave the maximum absorption and
determination of specific absorptivity), sample analysis (qualitative analysis and quantitative analysis), method
validation [11].
Preparation of Solvent
Hydrochloric Acid (HCl) 0.1 N was prepared by taken 8.5 ml of Hydrochloric Acid (HCl) 37%, inserted it into a 500
ml volumetric flask slowly through the walls of the flask, added 300 ml of purified water slowly through the walls of
the flask, shaken until evenly mixed, added with purified water until the mark line, and shaken until homogeneous.
Sodium Hydroxide (NaOH) 0.1 N was prepared by weighed 2.0 grams of Sodium Hydroxide (NaOH) Pellet, inserted
into a 500 mL volumetric flask, added 300 mL of purified water, shaken until dissolved, added with purified water

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until the mark line, and shaken until homogeneous.

Preparation of Standard Stock Solution

Standard Stock Solution was prepared out by weighed an amount of 50 mg of cimetidine, inserted into a 100 mL
volumetric flask, added 60 mL of solvent, sonicated for 15 minutes until dissolved, added solvent to the mark line,
and shaken until homogeneous (obtained stock solution with a concentration of 500 μg per mL).

Preparation of Standard Solution

Standard Solution was prepared by : pipetted 1 mL of stock solution, inserted into a 100 mL volumetric flask, added
solvent to the mark line, and shaken until homogeneous (obtained standard solution with a concentration of 5 μg per
mL).
Preliminary Analysis
Preliminary Analysis by measured the standard solution with an ultraviolet spectrophotometer in the wavelength range
of 200 nm to 400 nm, analysed the wavelength that gave the maximum absorption, analysed the absorbance at the
maximum wavelength of cimetidine in a solvent, and calculated the specific absorptivity of cimetidine in a solvent.

Determination of Regression Calibration Curve

Regression Calibration Curve was determined out by : pipetted 0.50 mL, 0.75 mL, 1.00 mL, 1.25 mL, and 1.50 mL
of stock solution, inserted into a separated 100 mL volumetric flask, added solvent to the mark line, and shaken until
homogeneous (obtained series standard solution with a concentration of 2.50 μg per mL; 3.75 μg per mL; 5.00 μg per
mL; 6.75 μg per mL; and 7.50 μg per mL). The series standard solution was measured with an ultraviolet
spectrophotometer at the wavelength range of 200 nm to 400 nm, analysed the absorbance at the maximum wavelength
of cimetidine in a solvent, also calculated the slope, intercept, and regression equation.

Sample Analysis
Sample Analysis was carried out by : weighed 20 tablets, crushed in a mortar with a pestle to obtained a fine powder,
weighed carefully an amount powder equivalent to 50 mg of cimetidine, inserted into a 100 mL volumetric flask,
added 60 mL of solvent, sonicated for 15 minutes until dissolved, added solvent to the mark line, and shaken until
homogeneous (obtained mixture with a concentration of 500 μg per mL). The mixture is filtered through a funnel and
filter paper, removed the first 10 mL of filtrate, collected the next filtrate, pipetted 1 mL of filtrate, inserted into a 100
mL volumetric flask, added solvent to the mark line, and shaken until homogeneous (obtained test solution with a
concentration of 5 μg per mL). The test solution was measured with an ultraviolet spectrophotometer at the wavelength
range of 200 nm to 400 nm, analysed the wavelength that gives maximum absorption for qualitative analysis, analysed

040017-3
the absorbance at the maximum wavelength of cimetidine in a solvent, also calculated the concentration and level of
cimetidine in tablet preparation samples for quantitative analysis.

RESULTS AND DISCUSSIONS

Development of analysis method of cimetidine by ultraviolet spectrophotometry with different solvent to determine
the effect of solvent on analysis of cimetidine by ultraviolet spectrophotometry. Figure 2 show the absorption spectrum
of cimetidine standard solution in acidic solvent and basic solvent at the wavelength range of 200 nm to 400 nm.

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FIGURE 2. The the absorption spectrum of cimetidine standard solution in acidic solvent and basic solvent at the
wavelength range of 200 nm to 400 nm

The wavelengths that give the maximum absorption of cimetidine in an acidic solvent and basic solvent have not been
published in the literature. The wavelength that gave the maximum absorption for cimetidine in acidic solvent was
218 nm. The wavelength that gave the maximum absorption for cimetidine in basic solvent was 220 nm. The obtained
cimetidine standard wavelength was used as a reference for qualitative analysis. The wavelength range that is allowed
and considered positive for qualitative analysis is ± 2 nm [12], which were 216 nm to 220 nm for acidic solvent and
218 nm to 222 nm for basic solvent.

These results are consistent with the molecular structure of cimetidine which has a chromophore group and an
auxochrome group, also the standard solution of cimetidine is a clear solution, colorless solution that provides
absorption in the ultraviolet region. The wavelength obtained is in the range of 200 nm to 400 nm which is the
ultraviolet light region [13].

The absorption of cimetidine at a concentration of 5 μg per mL in acidic solvent was 0.40279; the absorption
cimetidine at a concentration of 5 μg per mL in basic solvent was 0.42018. The results were further calculated on the
specific absorptivity (A11) of cimetidine in an acidic solvent and basic solvent respectively were 806 AU cm–1 %–1 dan
840 AU cm–1 %–1. The solvent affects the specific absorptivity and affects the wavelength that gives the maximum
absorption [14].

The analysis is continued with the determination of regression calibration curve which is used for quantitative analysis.
Figure 3 show the absorption spectrum of cimetidine series standard solution in acidic solvent and basic solvent at the
wavelength range of 200 nm to 400 nm. Table I show the absorbance of cimetidine series standard solution in acidic

040017-4
solvent and basic solvent at the wavelength that gave the maximum absorption (in acidic solvent was 218 nm and in
in basic solvent was 220 nm). Figure 4 show the calibration curve of cimetidine series standard solution in acidic
solvent and basic solvent at the wavelength that gave the maximum absorption (in acidic solvent was 218 nm and in
in basic solvent was 220 nm)

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FIGURE 3. The absorption spectrum of cimetidine series standard solution in acidic solvent and basic solvent at the
wavelength range of 200 nm to 400 nm

TABLE 1. The absorbance of cimetidine series standard solution in acidic solvent and basic solvent at the
wavelength that gave the maximum absorption (in acidic solvent was 218 nm and in in basic solvent was 220 nm)
X – Concentration Y - Absorbance (AU)
(μg per mL) Acidic Solvent Basic Solvent
2.50 0.20174 0.21119
3.75 0.30654 0.31510
5.00 0.40279 0.42018
6.25 0.50638 0.52615
7.50 0.60640 0.63450

040017-5
 Calibration Curve of Cimetidine Series Standard Calibration Curve of Cimetidine Series Standard
Solution in Acidic Solvent at 218 nm Solution in Basic Solvent at 220 nm

0.70 0.70
7.50; 0.63
0.60 7.50; 0.61 0.60

6.25; 0.51 6.25; 0.53

0.50 0.50
Absorbance (AU)

5.00; 0.42

Luas Area
0.40 5.00; 0.40 0.40

0.30 3.75; 0.31 0.30 3.75; 0.32

0.20 2.50; 0.20 0.20 2.50; 0.21

0.10 0.10

0.00 0.00
0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00
Concentration (μg per mL) Concentration (μg per mL)
Y = 0.0807 × X + 0.0011 Y = 0.0846 × X - 0.0016

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FIGURE 4. The calibration curve of cimetidine series standard solution in acidic solvent and basic solvent at the
wavelength that gave the maximum absorption (in acidic solvent was 218 nm and in in basic solvent was 220 nm)

The regression determination of the cimetidine series standard solution in the concentration range of 2.50 μg per mL
to 7.50 μg per mL in acidic solvent at the wavelength that gave the maximum absorption (218 nm) obtained a
coefficient of determination 0.9999 with regression equation Y = 0.0807 × X + 0.0011; and in basic solvent at the
wavelength that gave the maximum absorption (220 nm) obtained a coefficient of determination 0.9999 with
regression equation Y = 0.0846 × X - 0.0016. The coefficient of determination obtained meets the requirements that
not less than 0.90 [15]; which means that absorbance can be used for determination of concentration [16] and can be
used for quantitative analysis.
The analysis results of marketed cimetidine tablet preparation samples obtained the wavelength that gives maximum
absorption and the absorbance at the maximum wavelength of cimetidine in a solvent. Figure 5 show the absorption
spectrum of cimetidine test solution in acidic solvent and basic solvent in the wavelength range of 200 nm to 400 nm.

FIGURE 5. The absorption spectrum of cimetidine test solution in acidic solvent and basic solvent in the
wavelength range of 200 nm to 400 nm

All samples of cimetidine tablet preparations analyzed gave maximum absorption at wavelengths of 218 nm in acidic
solvent and 220 nm in basic solvent. Qualitative analysis by ultraviolet spectrophotometry was carried out by
comparing the wavelength that gave the maximum absorption from the sample analysed with the wavelength that gave

040017-6
the maximum absorption from the standard analysed [17]. The wavelengths obtained in the test solution analysis are
the same as the wavelengths obtained in the standard solution analysis, so that all the tablet preparation samples are
stated to contain cimetidine qualitatively. Table 2 show the levels of cimetidine in acidic solvent and basic solvent.
TABLE 2. The levels of cimetidine in acidic solvent and basic solvent
Cimetidine Levels
No. Sample
Acidic Solvent Basic Solvent
1. Cimetidine (Kimia Farma) 98.38 % ± 0.93 % 98.22 % ± 0.54 %
2. Cimetidine (Bernofarm) 100.24 % ± 0.95 % 100.47 % ± 0.55 %
3. Cimetidine (Ifars) 101.32 % ± 0.96 % 101.54 % ± 0.56 %
®
4. Omekur (Mutiara Mukti Farma) 99.11 % ± 0.94 % 99.29 % ± 0.55 %
5. Lexamet® (Molex Ayus) 100.74 % ± 0.95 % 100.56 % ± 0.55 %
6. Licimet® (Holi Pharma) 99.65 % ± 0.94 % 99.72 % ± 0.55 %

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7. Corsamet® (Corsa Industries) 101.09 % ± 0.96 % 101.23 % ± 0.56 %
8. Gastricon® (First Medifarma) 99.57 % ± 0.94 % 99.64 % ± 0.54 %

From the research results, that quantitatively all the cimetidine tablet preparations analysed had cimetidine levels in
the range of 98.38 % to 101.32 % for acidic solvent and 98.22 % to 101.54 % for basic solvent. These results indicate
that all cimetidine tablet preparations analysed were quantitatively meet the requirements for cimetidine levels listed
on the cimetidine tablet monograph in the Indonesian Pharmacopoeia, 6th edition, year 2020, which is the cimetidine
levels contained in the cimetidine tablet preparations not less than 90.0% and not more than 110.0% of the amount of
cimetidine stated on the label [18]. To test the validity of the results of the analysis, validation of the analytical method
that has been developed is carried out. Table 3 shows the recapitulation of analytical method validation with several
parameter.
TABLE 3. The recapitulation of analytical method validation with several parameter
Validation Results
No. Parameter
Hydrochloric Acid Sodium Hydroxide
1. Accuracy (Recovery Percentage) 99.67 % 100.04 %
2. Precision (Relative Standard Deviation Percentage) 0.72% 0.42%
3. Linearity (Coefficient of Correlation) 0.9999 0.9999
4. Range (μg per mL) 4 μg per mL to 6 μg per mL
5. Limit of Detection (μg per mL) 0.0399 μg per mL 0.0313 μg per mL
6. Limit of Quantitation (μg per mL) 0.1209 μg per mL 0.0951 μg per mL
7. Specificity Meet the Requirement

The results of the analytical method validation show that the developed method has good accuracy with the recovery
percentage being between 98.0 % to 102 % [19], good precision with the relative standard deviation percentage less
than 2 % [20], and good linearity with coefficient of correlation more than 0.999 [21]. The method have low limit of
detection and low limit of quantitation that indicates the method was sensitive enough. The range of 4 g per mL to 6
g per mL satisfies all validated accuracy parameter requirements. The specificity obtained from the satisfies
quantitative analysis from sample analysis, satisfies qualitative analysis from sample analysis, and satisfies validation
parameter [22].

040017-7
 CONCLUSIONS
The ultraviolet spectrophotometry method has been successfully developed for qualitative and quantitative analysis
of cimetidine compounds in tablet preparations using an acidic solvent and a basic solvent. The ultraviolet
spectrophotometry method has also been validated for the parameters of accuracy, precision, linearity, range, limit of
detection, limit of quantitation, and specificity. The method has been successfully applied for qualitative analysis and
quantitative analysis of cimetidine in marketed tablet preparation samples.

ACKNOWLEDGEMENT
The author would like to thank the institutions that have provided research funding which in this research was
supported by the Institut Kesehatan Deli Husada Deli Tua also to the institutions that provided material grants and
equipment loans which in this research were supported by Mutiara Mukti Farma Industri Farmasi.

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