TUGAS REVIEW JURNAL

ANALISIS FARMASI
ANALISIS OBAT ANTIVIRUS

Disusun Oleh :
Dwi Rizki Ersanella 180500170
Haka Pratama Ramadhan 180500127
Joni Yoga Pratama 180500132
Me’an Pesha Bryan Illahi 180500139
Rachmad Bagas Yahya Supriono 180500148

PROGRAM STUDI S1 FARMASI

FAKULTAS ILMU-ILMU KESEHATAN
UNIVERSITAS ALMA ATA
YOGYAKARTA
2022
Analysis Of Drugs Antiviral By Cromatography and Spectrophotometry : Comparative
Review

1. Abstract
Viral infection is defined as a disease caused by a pathogen in the form of a virus that
arises through transmission from an infected person, infected animals, or contaminated
inanimate objects to susceptible hosts. Some of the methods used in the journals reviewed
are: UV spectrophotometer, Gas chromatography, Mass spectroscopy, High Performance
Liquid Chromatography (HPLC). The purpose of this journal review is to see what
methods are often used in analyzing antiviral drugs. The method used in the journal above
can now be considered simple, fast, and easy to apply, so it is very suitable for analyzing.
On the UV method, this method is more sensitive and accurate to determine the sample
quantitatively where this method can reduce unnecessary and tedious sample preparation.
The results of this journal review, researchers mostly use the UV spectrophotometric
method, this is because this method is more effective, sensitive and accurate to determine
the sample quantitatively where this method can reduce unnecessary and tedious sample
preparation.
Keywords: Antiviral, Gas chromatography, HPLC, Mass spectroscopy, Specthrofotomerty,
UV, Viral Infectious, Oseltamivir, Raltegravir, Triazid, Aclycovir, Daclatasvir,
Pibrentasvir, Glecaprevir
2. Introduction
In the last few decades, viral infectious disease is a global health problem that affects
public health systems and economies worldwide (Graham and Sullivan 2018). Viral
infections can occur at any time and are not limited to a certain age, race, or gender. As
intracellular parasites, viruses can invade various organs in the human body and other
species, causing various types of disease, from mild to severe. For example, infection by
four types human coronavirus ( ₂₂₉E, NL6₃, OC43, and HKU₁) which can cause mild to
moderate respiratory tract infections (herpes simplex virus 1 and 2 (HSV-1 and HSV-2) on
the skin to infections of the internal organs by hepatitis and HIV viruses which are still a
global threat. In fact, since the end of 2019 until now, the world's population is still

2
threatened by the presence of SARS-CoV-2, a new type of coronavirus that causes the
COVID-19 pandemic. (Usmar et al., 2021)
Viral infection is defined as a disease caused by a pathogen in the form of a virus that
arises through transmission from an infected person, infected animals, or contaminated
inanimate objects to susceptible hosts (Usmar et al., 2021). In general, the control of
infectious diseases caused by viruses has begun to progress. This is achieved through
increasing global public awareness in the sanitation aspect, improving the quality of
medical care, and the widespread development of new vaccines and antivirals from various
biological sources as one of the immunopharmacology and immunotherapy efforts.
(Graham dan Sullivan, 2018)
Every day our bodies interact with various objects that tend to be comfortable places
for harmful bacteria, viruses, fungi, and parasites to live. These microorganisms can cause
disease and often this leads to death (Medzhitov, 2007; Murphy, 2011). In 2005, Indonesia
was shocked by cases of avian influenza infection caused by the H5N1 virus, a very
dangerous type A influenza virus strain. On a global scale, the H1N1 virus, which is also a
close relative of the H5N1 virus, claimed a number of victims in America in 2009. In
addition, in the period 2013-2016, the Ebola virus spread terror deaths on the African
continent with more than 28,000 cases and almost half ended in death. (Coltart et al., 2017)
The three viruses are viruses with an RNA genome with a fairly high mortality rate. In
addition to RNA viruses, several viruses with a DNA genome such as hepatitis B virus
(HBV) and various types of herpes viruses (human herpes virus, HHV 1-8) has been
reported to cause certain diseases in humans ranging from mild infections that can be
treated with antiviral medication to cancer that is difficult to cure. (Arfiansyah, 2017)
Viral and microbial infections are one of the most important life-threatening problems.
The emergence of new viral and bacterial infectious diseases increases the demand for new
therapeutic drugs. Medicinal plants contain various natural compounds that have strong
antiviral activity. Further synthesized green SNPs can enhance the therapeutic applicability
of plants and may be a source of novel antiviral agents. These SNPs are safe and have a
multivalent function, which makes them less likely to encounter resistant viruses. SNPs can
also access viral cells and exert their antiviral activity through interactions with viral
genomes (RNA or DNA) or through inhibition of pathways important for viral replication

3
 and it has been reported that SNPs exhibit antiviral activity against many viruses, such as
herpes simplex virus, hepatitis B, and flu H1N1 (Elshamy et al., 2019).
Tenofovir has emerged as a promising drug for the treatment of Covid-19 infection in
September 2020. Extension and molecular docking reaction studies have shown that
tenofovir, remdesivir, and other nucleoside reverse transcriptase inhibitors can be effective
against Covid-19 by inhibiting RNA polymerase, as long as they reach high intracellular
concentrations in target tissues (Akbel dan Bulduk, 2021).
Favipiravir is a prodrug derived by chemical modification of the pyrazine moiety of T-
1105. Favipiravir is rapidly emerging as the main choice for the treatment of COVID-19
due to the absence of a definitive treatment and much emphasis on reusing existing drugs
as developing new drugs will take years. Favipiravir is a viral RNA polymerase inhibitor
that prevents the replication of the viral genome. RNA polymerase is an enzyme that is
essential for viruses to make copies of themselves in the body. It selectively targets this
enzyme, to inhibit the replication of the virus in the body. Favipiravir is an effective
antiviral drug and has a wide range of formulations developed to treat different viruses
(JYOTHI B dan KAVYA R, 2021), figure of Favipiravir structure shown in figure 4
3. Experimental Section
3.1. Methods
UV spectrophotometer is a tool used to measure the relative energy if the energy is
transmitted, reflected or emitted as a function of wavelength. The advantage of
spectrometers over photometers is that the wavelength of white light can be more
selected and this can be obtained with a parsing device such as prisms, gratings or
optical slits.
Gas chromatography can be used to test the purity of certain materials. Apart from
this gas chromatography can be used to separate the various components of a mixture.
In some cases, gas chromatography can be used to determine complex compounds.
Mass spectroscopy (mass spectrometry) in the form of a mass spectrum obtained
by converting a compound of a sample into fast-moving ions which are separated on
the basis of their mass-to-charge ratio. Mass spectroscopy is capable of producing a
beam of ions from a test substance, sorting these ions into a spectrum according to the
mass to charge ratio and recording the relative abundance of each type of ion present.

4
 In general only positive ions are studied, because ions The negative resulting from the
source of the collision is usually small.
High Performance Liquid Chromatography (HPLC), is a liquid chromatography
(LC) technique used for the separation of various components in a mixture. HPLC is
also used for the identification and quantification of compounds in drug development
processes and has been used worldwide for decades.
Purpose The use of HPLC is to separate molecules in a minimum of time
(Behnoush, 2015), so it is important to improve analysis results and reduce analysis
time. The simplest method available for shorten the analysis process is shorten the
column length and increase the flow rate. This approach, however, it can be risky,
because the mix complex of compounds will not be separated adequately and the
column efficiency will be much lower. The second way to shorten analysis time is to
reduce particle size. This allows analysis high speed with high efficiency, but the
negative aspect is the generation of back pressure unacceptable high for the system
Conventional HPLC and analytical columns conventional.
Emerged an instrumentation called UHPLC which offers high efficiency in
analysis. Ultra-high-performance liquid chromatography (UHPLC) involves the
separation of LCs using columns containing particles smaller than the 2.5-5-μm size
typically used in HPLC. The benefit of using a column containing smaller particles
(usually sub-2 m) is the greater efficiency per unit time (Chawla, 2016).
4. Conclusion
The method used in the journal above can now be considered simple, fast, and easy to
apply, so it is very suitable for analyzing In the UV method, this method is more sensitive
and accurate for quantitative knowing of samples where they reduce the preparation of
samples that are not necessary and tedious.
5. Acknowledgement
The author would like to thank the researchers who have conducted research so that
we can conduct a journal review. Thanks also to Mr. Muhammad Rahman as LNO for
Pharmacy Analysis, a lecturer at Alma Ata University Yogyakarta who has guided in
reviewing journals about antivirus.

5
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7. Figure

(Figure 2). Chemical structure

(Figure 1). Chemical structure of pibrentasavir of glecaprevir

(Figure 3). Chemical structure of

Stavudine (Figure 4). Chemical structure
of Tenofofir

10
 (Figure 5). Structure of Famciclovir (Figure 6). Amantadine
hydrochloride (AMD).

(Figure 8). Chemical structure

(Ffigure 7). Scheme for the reaction pathway of of (A) Tenofovir disoprosi
GTHC with MBTH fumarate (B) Lamvudine

(Figure 10). Chemical structure

(Figure 9). Molecular structure (oseltamivir)
of Ribavirin

(Ffigure 11). Chemical structure οf Daclatasvir

(Figure 12). Molecular structure
and Sofosbuvir
(oseltamivir)

11
 Methyldopa

Terbutaline sulfate
(Figure 14). Structure of
(Figure 13). Chemical structure οf Methyldopa
Nucleosides of active
and Terbutaline sulfate
compound of mushroom
(Adenosine and Cordicepin)

(Figure 15). Chemical Structure of (A) Tenovir Disoproxil fumarate (B)

Lamivudine

12
 (Figure 16) Chemical Structure TFV,TAF and CMX157

(Figure 17). Chemical Structure Simeprevir

(Figure 18). Proposed fragmentation pathway for the simeprevir protonated

degradation product

13
 (Figure 19). Structures of the studied drugs

(Figure 20). Chemical structure οf DCL and SOF.

(Figure 22). Tenofovir disoproxil

(Figure 21). Molecular Structure Of
fumarate This
Didanosine

14
 (Figure 23). THE STRUCTURE OF (Figure 24). Chemical structure of
Famciclovir
EFAVIRENZ Systematic

(Figure 25). Chemical structure of (a)

ledipasvir and (b) sofosbuvir
either

8. Table

Antivirus Instrumenta Detector LOD Linier Reference

l Applied (µg/ml) Range
(µg/ml)
Oseltamivir HPLC UV/LC 1.2 10 – 60 (Gungor et al.,
(Tablet) 0.4 2021)
Raltegravir HPLC UV 20 1, 2, 3, 4, 5 (Deepthi et al.,
2021)
Triazid HPLC UV/IR (Conversions
et al., 2021)
Aclycovir 10, 20, 30, (Chandravansh
40, 50, 60 i et al., 2021)
Daclatasvir/ HPLC UV 0.15 5, 10, 15, 20, (Jain et al.,
Sofosbuvir 25 2019)
0.570
Daclatasvir HPLC UV 1.25 10, 20, 30 (Blue et al.,
2017)

15
Pibrentasvir, HPLC UV 0.273 10 - 80 and (Saroja et al.,
Glecaprevir 25 - 200 2019)
0.950
Gemcitabine HPLC UV-Vis 0.297 10 – 100 (Profile, 2018)
HCl
Amantadine UV 0.12 and 0.4 – 9.60 (Omara dan
HCl 0.18 Amin, 2011)
Famciclovir HPLC UV-Vis 0.14 2, 4, 6, 8, 10, (Sy dan T,
(Tablets) 12 2021)
Lampranthu Spectrophoto UPLC- - - (Elshamy et
s metry UV- MS al., 2019)
coccineus VIS
dan
Malephora
lutea F.
Aizoaceae
Favipiravir Spectrophoto UV-Vis 0.095 μg/ml 0-10 μg/ml (JYOTHI B
metry (UV dan KAVYA
JAPAN R, 2021)
1801)
Tenofovir HPLC UV-Vis 2.30 μg 10, 20, 30, (Akbel dan
mL⁻¹ 40, 50 and 60 Bulduk, 2021)
µg mL⁻¹
Sofosbuvir Spectrophoto HPLC 0.094 0.500-100 (El-Yazbi,
metry dan and UV μg/mL μg/ml 2017)
chromatograp
hic
Emtricitabin Spectrophoto UV-VIS EMT: 2-40 µg/mL (Ashour dan
e and metry 0.4372 Belal, 2017)
tenofovir TEN:
disoproxil 0.6009
fumarat

Sofosbufir Spectrophoto Shimadz 0.06 and SOF: 0.2-3.0, (Saad et al.,

and metry u 0.15 µg/ml 0.2-4.0 2021)
Daclatasvir UV/Vis DAC: 0.5-4.5
and 0.5-5.0
μg/ml
Pomegranat HPLC UV - - (Salles et al.,
e 2021)
Mammea Chromatogra MTT - 400-6.25 (Gómez-
americana phic μg/mL Calderón et al.,
and 2017)
Tabernaem
onta cymose
Acyclovir Spectrophoto Shimadz 0.3 mcg/ml 30 µg/ml (Ajima dan

16
 metric u UV- Onah, 2015)
Visible
Remdesivir Chromatogra HPLC DAD: 0,03 0.1-15 μg/mL (Khairani,
phic FD: 0,015 Nasif dan
Muchtar,
2013)
UV -
Oseltamivir (Gungor et al.,
HPLC Visible 1.2 10–60
dan Enfluvir 2021)
(Deepthi et al.,
Ribavirin HPLC UV 0.026 5-40
2021)
Daclatasvir Spectrοphοtο UV - 0.6950 2.5– 25.0 (Eissa et al.,
meter mοdel Visible
Sofosbuvir 1.7646 10.0 – 80.0 2020)
V-630
(Marzouk et
Favipiravir HPLC-DAD UV 1.02 6.25 – 250.00
al., 2020)

Methyldopa 0.026 0.08 - 0.48

UV - (Nanoparticles,
Spectroscopy
Terbutaline Visible 2021)
0.013 0.04 - 0.6
sulfate
Aristolochic UHPLC–Q/ 0.08–2 & (Yu et al.,
MS 0.19 & 0.09
acid I & II TOF 0.04–2 mg/L 2022)
50–250 ng (Selcuk et al.,
Lamivudine 2.23
spot–1 2021)
HPTLC UV
100–500 ng
Zidovudine 2.90
spot–1
Adenosine 0.004 (Srivastava,
HPLC MS - Srivastava dan
Cordyecipin 0.005
Singh, 2021)
(Extraction et
Efavirenz UHPLC MS 3 -
al., 2021)
Chlorogenic Spectrometry (Aktepe et al.,
MS 0.065 0.250–2
acid LC 2021)
Sofosbuvir HPLC TLC/MS VPS = 1–50 μg/mL (Alqahtani et
3,122 and 5–80 al., 2020)
and
SFV = 8412 μg/mL were
Velpatasvir obtained for
VPS and
SFV
Favipiravir HPLC UV Spectrophot 10-60 μg/mL (Bulduk, 2021)
ometric ‾ˡ
Method :
1.4/4.3
Liquid
Chromatogr
aphic

17
 Method :
0.4/1.1
Daclatasvir HPLC UVDS DAC= 0, 16 2 -200 (S. Eldin et al.,
SOF= 0, 10 µg/mL‾ ˡ 2017)
and
Sofosbuvir
Simeprevir RP-HPLC UV 07659 2.5-40 µg/mL (Attia et al.,
2018)
Tenofovir (LC – MS / MS - 0.030/1.00, (Hummert et
0.06/2.00, al., 2018)
MS)
0.250/5.00,
1.00/10.0,
5.00/25.0,
25.0/50.0,
75.0/100, and
150/200
µg/mL
Sofosbuvir, HPTLC/ UV SFS= 23,5 100, 150, (Saraya,
LAM = 30 250, 400, 500 Elhenawee dan
Lamivudine, HPLC
RIT = 21,5 µg/mL Saleh, 2021)
and
Ritonavir
Lamivudine HPLC UV LAM = 5-25µg/mL (Pednekar dan
0,85 Kudchadkar,
and
TDF= 1, 12 2015)
Tenofovir
Disproxil
Fumarate
Darunavir, HPLC UV– 0,08 3–8 ppm (Acquavia et
al., 2020)
indinavir, Vis / MS
lopinavir,
ritonavir,
saquinavir,
favipiravir,
remdesivir
and
galidesivir.
Simeprevir FTIR UV 0,016 0.05–1.0 (Mohammed
μg/mL et al., 2020)

18
ledipasvir HPLC UV LED = 0, 13 2–50 μg/mL ‾ (EL-Shorbagy
SOF = 0,8 ˡ et al., 2018)
and
sofosbuvir
Tenovofir HPLC/UPLC UV/MS 1.51 10-100 (Tiris, Çiloğlu
1.31 dan Erk, 2020)
2.32
Daclatasvir Spectroscopy UV/MS 0.858 2, 4, 6, 8, 10, (Mohammed,
12 Adam dan
Shantier, 2017)
Ledipasvir HPLC UV-Vis 2 – 25 (Abdelwahab
2 – 50 dan Farid,
2016)
Famciclovir UV 0.068 0 – 80 (Mondal et al.,
2018)
Didanosine HPLC UV 4.29 25 – 150 (Ramesh dan
Rao, 2015)
Daclatasvir Spectroscopi 0.43 1.0 - 10.0 (Mohammed
c et al., 2020)
Daclatasvir, HPLC/UVDS Uv 0,16 80, 100, 120 (S. Eldin et al.,
Sofovubir 0.10 2017)

0.15
0.16
Daclatasvir, HPLC Uv 0.19 1 – 20 (Atia et al.,
Sofovubir 2018)
Efavirenz HPLC UV/ 1.0, 1.5, 2.0, (Reddy and
CCM/ 2.5, 3.0, 4.0 Gillella, 2012)
SPS/DPS
Atazanvir, HPLC/ SEM Uv-Vis 5-30 0.0853 (Syed, Marathe
Ritonavir 15-90 0.8314 dan
Mahaparale,
2020)

19