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Medicinal & Analytical Chemistry International Journal Research Article 9 min read

Literature Review on Spectrophotometric, Chromatographic and Voltammetric Analysis of Ivermectin

Sebaiy MM*, Shanab AG, Nasr AK, Hosney AE, Elsaid AG and Ramadan AH
* Corresponding author
ISSN: 2639-2534  10.23880/macij-16000170  Received: June 20, 2021  Published: July 20, 2021
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Keywords
Ivermectin Degradation Products Biological Samples Literature Review COVID-19
Abstract

We will present the majority of the most recent published methods for determining the anti parasitic drug, Ivermectin in its pure form, combined form with other drugs, combined form with degradation products, and in biological samples in this literature review. This review also deals with the effectiveness of Ivermectin in treatment of COVID-19.

Introduction

Ivermectin (IVM) is an orally effective microfilaricidal agent that is a synthetic derivative of the antiparasitic family of compounds known as avermectin E. It is currently the most effective treatment for patients infected with the nematode Onchocerca volvulus, which is a leading cause of blindness in tropical areas. It’s a macrolide endectocide that works on all endoparasites with cutaneous tropism (Strongyloides stercoralis, Ancylostoma braziliense, Cochliomyia hominivorax, Dermatobia hominis, Filaria bancrofti, Wucheria malayi, Onchocerca volvulus Loa-loa) and ectoparasites [1]. IVM is an antiparasitic drug with a wide range of activity, high effectiveness, and a high safety margin. This compound has been widely used in veterinary medicine since 1987, and its use in humans has been expanded [2]. IVM is supplied orally in a single dose of 150 mg/kg once a year. IVM is usually well tolerated, with the exception of a few extreme serious reactions such as significant systemic postural hypotension. When compared to diethylcarbamazine and suramin, which were commonly used to treat onchocerciasis, the medication has strong advantages in terms of ease of administration and tolerability. As a result, IVM is appropriate for use in mass- care programmes and is the most effective treatment choice for onchocerciasis currently available. As a result, it gives hope to tens of thousands of people who are on the verge of going blind, and it makes a significant contribution to tropical medicine [3]. The drug was developed as a result of a one-of-a-kind international partnership between the public and private sectors. In addition, the implementation process included the world’s first and largest drug donation initiative, as well as a unique collaboration between governments, non- governmental organisations, and industry. The drug is now being used in two global disease-eradication programmes that support millions of the world’s poorest people for free [4]. IVM activates unique IVM-sensitive ion channels in invertebrates, causing an influx of Cl-ions through the cell membrane. Muscle paralysis occurs as a result of the resulting hyper-polarization [5]. Due to the current importance of this drug in treatment of pandemic COVID-19, this literature focuses on its mode of action and different analytical methods that have been developed for determination of this drug in different pharmaceutical and biological samples.

IVM and Covid-19

Importin (IMP/1) binds to the coronavirus cargo protein in the cytoplasm (top) and translocates it into the nucleus through the nuclear pore complex (NPC), where the complex disintegrates and the viral cargo reduces the host cell’s antiviral response, allowing for increased infection. IVM binds to the IMP/1 heterodimer and nucleus. This leads to less inhibition of antiviral responses, resulting in a more natural and effective antiviral response [6].

Figure 1: Chemical structure of IVM.
Click to enlarge
Figure 1: Chemical structure of IVM.

Review of Analytical Methods

Various techniques were used for the analysis of IVM in

Spectrophotometric Methods

its pure form, combined forms, pharmaceutical formulations, and in biological fluids. The available reported methods in this literature can be summarized as follows:

LODLinearity rangeλ
max
(nm)		Method or ReagentMatrixDrugRef
---5-40 µg/mL314.4UV SpectrophotometryTabletIVM[7]
---10-200 μg/ mL485Visible
spectrophotometry		Oral suspension
and injection		Triclabendazole and IVM[8]
µg/mL
0.029		5-15 µg/mL245Multivariate
Spectrophotometry		TabletIVM[9]
2.274
µg/mL		1.2-7.2 μg/mL245UV SpectrophotometryTabletLevocetirizine and IVM[10]
---5-40 µg/mL314.4UV SpectrophotometryTabletAlbendazole and IVM[11]

Chrmoatographic Methods

HPLC methods

DrugsMatrixColumnMobile phaseDetectorLinearity
range		LODRef
IVMMeat and liverμ- Bondapak C
18		Acetonitnie and waterfluorescence
detection		---250 pg[12]
IVM,
FEBANTEL,
PRAZIQUANTEL,
PYRANTEL
PAMOATE		TabletsC column (50
8
x 2.1 mm i.d)
coupled with
a C8 (10 x 2.1
mm i.d) guard
column		Water/acetonitrile (15:85
v/v) containing 0.1%
formic acid and 3 mmol/L
ammonium formate		MS/MS40-200 ng/mL0.5 ng/
mL		[13]

IVM Liver Bond‐Elut C8 column Methanol:water (96:4 v/v) fluorescence detection 2.48 - 24.8 ng per g tissue 1 ng per g tissue [14]

Hypersil Gold C18 column (150 x 4.6 mm, 5 microm particle size) Acetonitrile, methanol and distilled water (50:45:5, v/v/v) IVM Human plasma triclabendazole and IVM Pharmaceutical Formulation C18 RP column Acetonitrilemethanol wateracetic acid (56 36 7.5 0.5, v/v/v/v) UV at 245 nm 27.01-81.02 µg /mL 0.07 µg / mL [16]

IVM Reindeer feces C18 solid-phase extraction column Acetone, isooctane Fluorescence detection clorsulon, albendazole, triclabendazole and IVM

120 mM sodium dodecyl sulfate, 15% propanol and 15 mM phosphate buffer (pH 5.5)

Pharmaceutical preparations Monolithic column

IVM Milk SPE C18 column and SPE silica column IVM Animal tissues SPE C18 columns 95:5 v/v methanol:water Fluorescence detection 10-120 ng/g 2 ng/g [20]

IVM Pig serum Phenomenex C18 (5 microm, 250 mm x 4.6 mm) IVM Plasma Supelcosil LC-18 column Acetonitrile and water (96:4, v/v) UV detection 1 - 40 μg/L 0.5 μg/L [22]

RP column (C18, 250 × 4.6 mm, 5 μm) with a security guard column (C18, 10 × 4 mm, 5 μm) (Phenomenex, Torrance, CA) IVM Plasma IVM Cattle and Sheep Tissues IVM Animal liver : cattle, goats, sheep and swine Selectosil C18 (5 mm, 250 £ 4.60 mm) reverse- phase column Acetic acid (0.2% in water), methanol and acetonitrile (4:40:56 v/v/v) IVM and moxidecin Bovine milk IVM Meat samples RAMIP-BSA column methanol:water (70:30, v:v) UV detection 50-500 μg/ kg 16.66 μg/ kg [27]

Fluorescence detection 3-13600 µg/L 1 µg/L [15]

5−2000 ng/g wet weight feces. --- [17]

UV at 225 nm 30–300 µg/ mL 6.15 µg/ mL [18]

Acetonitrile, water and triethylamine Fluorescence detection 2.8-55.6 ng/ mL 0.5 ng/ mL [19]

Methanol and water in the ratio of 90:10 (V/V) Fluorescence detection 0.010-20 mg/L 0.010 mg/L [21]

Methanol and water (90:10) UV detection 20–1000  ng/ mL --- [23]

Du Pont Zorbax ODS (4.6 mm X 15 cm Methanol-water (95:5) UV detection --- 1-2 ppb [24]

SPE C8 and silica gel columns Methanol–water (98 : 2) Fluorescence detection 7.5–30 ng/g 2.5 ng/g [25]

Fluorescence detection 0.1-50 ng/mL 0.033 ng /mL [26]

Waters Xbridge C18 column (250 4.6 mm i.d., 5 mm) with a guard column (20 4.6 mm i.d., 5 mm) abamectin (ABA), emamectin (EMA) benzoate and IVM (IVM) Rice HPLC methods Acetonitrile/ methanol/ water (10 : 80 : 10, v/v/v) Fluorescence detection 0.01 - 5 µg/mL 1.3 µg/ kg [28]

DrugMatrixStationary phaseMobile phaseDetectorLinearity
range		LODRef
IVMTabletsLichrospher TLC
aluminum plates
pre-coated with
silica gel 60F-254
(20cm×10cm×200 :m)		n-hexane: acetone:
ethylacetate (6.5:
3.5: 0.1 v/v/v)		UV at 247
nm		100-5000
ng/spot		8.22ng/
spot		[29]
IVM and
Albendazole		Tabletsaluminum-backed silica
gel 60 F254 layers		toluene-ethyl
acetateglacial
acetic acid, 6:4:0.5
(ν/ν/ν))		UV at 247
nm		0.12 - .54
µg/band		0.02 µg/
band		[30]
Closantel
and IVM		VialsSilica gel 60 F254 plateToluene:
isopropanol:
ammonia 33%: 11
glacial acetic acid
(70:28:10:1, by
volume)		UV at 245
nm		0.06-3 µg/
band		0.013
µg/band		[31]

Voltammetric Methods

DrugmatrixelectrodelinearityLODRef
IVM and levamisolein
anthelmintic and
urine samples		Pharmaceutical
formulations and urine		Cathodically pretreated boron-
doped diamond electrode		0.60–50
μmol/L		0.30 μmol/L[32]
IVMUrine and tape waterSilver nanoparticles (AgNPs)
modified boron and sulfur co-
doped reduced graphene oxide
(B, S@rGO)		0.3-60.0
nM		0.1 nM[33]

Conclusion

This literature review represents an up to date survey about all reported methods that have been developed for determination of Ivermectin in its pure form, combined form with other drugs, combined form with degradation products, and in biological samples such as spectrophotometry, liquid chromatography, voltammetry, etc.

References

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@article{sebaiy2021,
  title   = {Literature Review on Spectrophotometric, Chromatographic and
Voltammetric Analysis of Ivermectin},
  author  = {Sebaiy MM, Shanab AG, Nasr AK, Hosney AE, Elsaid AG and Ramadan AH},
  journal = {Medicinal & Analytical Chemistry International Journal},
  year    = {2021},
  volume  = {5},
  number  = {2},
  doi     = {10.23880/macij-16000170}
}
Sebaiy MM, Shanab AG, Nasr AK, Hosney AE, Elsaid AG and Ramadan AH (2021). Literature Review on Spectrophotometric, Chromatographic and
Voltammetric Analysis of Ivermectin. Medicinal & Analytical Chemistry International Journal, 5(2). https://doi.org/10.23880/macij-16000170
TY  - JOUR
TI  - Literature Review on Spectrophotometric, Chromatographic and
Voltammetric Analysis of Ivermectin
AU  - Sebaiy MM, Shanab AG, Nasr AK, Hosney AE, Elsaid AG and Ramadan AH
JO  - Medicinal & Analytical Chemistry International Journal
PY  - 2021
VL  - 5
IS  - 2
DO  - 10.23880/macij-16000170
ER  -