Abstract
In this literature review, we will introduce most of up-to-date reported methods that have been developed for determination of lamivudine in its pure form, combined form with other drugs, combined form with degradation products, and in biological samples.
Author Contributions
Academic Editor: Fatma Mohammed Mady, Department of Pharmaceutics, Minia University, Egypt.
Checked for plagiarism: Yes
Review by: Single-blind
Copyright © 2021 Roshdy E. Saraya, et al.

Competing interests
No author has any associations that may represent a potential conflict of interest.
Citation:
Introduction
Lamivudine
(LAM) is an analogue of cytidine. It can inhibit both types HIV-1 and HIV-2 reverse transcriptase and also the reverse transcriptase of hepatitis B virus. It is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis 1. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated 2.
As such, in this literature review, we will introduce most of up-to-date reported methods that have been developed for determination of LAM in its pure form, combined form with other drugs, combined form with degradation products, and in biological samples.
Review of Analytical Methods
Various techniques were used for the analysis of RIT in pure forms, in their pharmaceutical formulations and in biological fluids. The available reported methods in the literature can be summarized as follows: Table 1.
Table 1. Spectrophotometric MethodsDrugs | Method or reagent | λmax | Ref |
LAMand zidovudine | First drivative spectrphotometry | 239.5 and 245.3 nm for LAM and 225.1 and 251.5 nm for zidovudine | 3 |
LAM and stavudine | First drivative spectrphotometry | 280 for stavudine and 300 nm for LAM. | 4 |
LAM and stavudine | 3-methyl-2-benzothiozolinone hydrazone hydrocloride and ferric chloride | 660 nm for LAM and 630 nm for stavudine | 5 |
LAM | chloramine-T and methyl orange, or chloramine-T and indigo carmine | 520nm or 610nm | 6 |
LAMand zidovudine | derivative spectrophotometry | 246 nm for LAM and 263 nm for zidovudine | 7 |
LAM | N HCl0.1 N NaOH | 279.6 nm269.8 nm | 8 |
Tenofovir, Disoproxil and LAM | Simultaneous equation methodMulticomponent analysisDerivative spectroscopy method | 247, 259 and 272 nm | 9 |
LAMand zidovudine | Derivative Spectrophotometry | 242, and 236 nm | 10 |
LAM | methyl orange and indigocarmine | 520n and 610 nm | 11 |
LAMand zidovudine | UV spectroscopy and multivariate calibration | 250 and 267 nm | 12 |
LAM and efavirenz | overlain spectra method | 271 and 247 nm | 13 |
LAM | chloranilic acid and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone | 221 and 230 nm | 14 |
LAM, nevirapine and zidovudine | overlain spectra method | 280.2nm, 312nm and 266.8nm | 15 |
LAM, Sofosbuvir,and Ritonavir | Silver nanoparticles synthesis | 421 nm for Sofosbuvir and Ritonavir and at 425 nm for Lamivudine LAM | 16 |
2. Chromatographic Methods
Matrix | Column | Mobile phase | system | Ref |
---|---|---|---|---|
plasma | Aquasil C18 column | ACN : water (15:85 v/v) | HPLC–MS/MS | 17 |
Tablet | Spherisorb® C18 analytical column | methanol: water: ACN (70:20:10 (v/v/v)) | HPLC-UV 265 nm | 3 |
plasma | a Shim-pack® C8 column | Sodium dihydrogen phosphate monohydrate (10 mM): methanol:ACN (94:3:3, v/v/v, pH 4.8) | HPLC-UV 270 nm | 18 |
plasma | Phenomenex C8 column | A gradient elution with 20 mM ammonium acetate buffer with pH 4.5 : ACN | HPLC–MS/MS | 19 |
Tablet | Symmetry C18 column | methanol: water (20:80 v/v) | HPLC-UV 270 nm | 4 |
Tablet | C18 column | A gradient elution with 80% of 10 mM acetate buffer (pH 3.5): 20% methanol: 50% CAN: 50% isopropyl alcohol. | HPLC-UV 270 nm | 20 |
Plasma and saliva | Zorbax SB-C18 column | 0.005 M di potassium hydrogen phosphate solution in water (pH 6.8): methanol (92:8 v/v). | HPLC-UV 270 nm | 21 |
Tablet | HiQ SilC18 column | 0.01 M potassiumdi hydrogen orthophosphate (pH 3.0): methanol (55:45 v/v) | HPLC-UV 272 nm | 22 |
plasma | C18 column | a mixture of phosphate buffer (0.05 M) containing TEA (1 mL/L pH 3.5): methanol (91:9, v/v) | HPLC-UV 276 nm | 23 |
plasma | Lichrospher® RP‐ C18 column | 20 mM ammonium acetate: methanol containing 1% of acetic acid (60:40 v/v) | HPLC–MS/MS | 24 |
plasma | a phenyl column with Phenomenex C18 guard column | 5% methanol in 20 mM dibasic phosphate buffer (pH 6). | HPLC-UV 256 nm | 25 |
plasma | octylsilane column | 20 mM sodium phosphate buffer with (8 mM 1 octane sulfonic acid sodium salt): ACN (86:14, v/v) | HPLC-UV 265 nm | 26 |
plasma | C18 analytical column | CAN: water (9:91, v/v) | HPLC-UV 271 nm | 27 |
plasma | Aquasil C18 column | ACN: water (15:85, v/v) | HPLC–MS/MS | 28 |
plasma | A Symmetry Shield RP C18 column | A gradient elution with acetate buffer (20 mM potassium acetate pH 4.60): ACN | HPLC-UV 260 nm | 29 |
plasma | a Shiseido C8 column | a gradient elution with methanol: water (80:20, v/v) and water, both containing 10 mM ammonium acetate | HPLC –MS/MS | 30 |
Plasma | a Spherisorb® C18 analytical column | methanol: water (75 : 25, v/v) | HPLC-UV at 265 nm | 31 |
Plasma | a C18 column | CAN: water (13:87, v/v) | HPLC-UV at 220 nm | 32 |
Tablet | Thermo Hypersil Gold C18 column | Agradiant elution with 20 mM sodium phosphate buffer (pH 3.5) with phosphoric acid : methanol | HPLC-UV at 265 nm | 33 |
Plasma | a C18 column | 0.01M sodium dihydrogen phosphate : methanol: ACN (4 : 2 : 3 v/v/v) | HPLC-UV at 285 nm | 7 |
Plasma | Phenyl column C18 column | ACN: 0.085% phosphoric acid (12:88, v/v) | HPLC-UV at 270 nm | 34 |
Plasma | Aquasil® C18 | A gradient elution with 0.05% FA in either water or methanol | HPLC – MS/MS | 35 |
Plasma | Zorbax® C18 column | methanol: water: phosphate buffer (pH 5.65) (80:10:10; v/v/v) | HPLC-UV at 275 nm | 36 |
Plasma | A Phenomenex C18 | Methanol: Water (85:15%v/v) | HPLC-UV at 270 nm | 37 |
Plasma and tissues | a phenyl column | 8% ACN in 5 mm 1‐heptane sulfonic acid dissolved in 30 mm AF buffer (pH 3.3). | HPLC-UV at 254 nm | 38 |
Plasma | a Vydac C18 column | A gradient elution, both CAN and ultrapure water solvents contained 0.2% FA. | HPLC – MS/MS | 39 |
Rabbit plasma | Hypersil BDS C-18 column | 0.25% Triethylamine buffer (pH 3.0): CAN (70:30, v/v) | HPLC-UV at 256 nm | 40 |
Plasma | Zorbax SB C8 column | A gradient elution with methanol: acetic acid sodium acetate buffer (pH 3.9) | HPLC-UV at 260 nm | 41 |
Plasma | Prontosil C18 column | 1 mM ammonium acetate in water (pH 6.5 ± 0.3): ACN (50:50 v/v) | HPLC – MS/MS | 42 |
Plasma | A Chromolith C18 column | 50 mM sodium dihydrogen phosphate : TEA (996:4 v/v) | HPLC-UV at 278 nm | 43 |
Plasma | An ACE 5 CN column | 0.5% FA in water: ACN (55:45, v/v) | HPLC – MS/MS | 44 |
Rat tissue | a C18 column | methanol: 7.5 mM ammonium acetate (30:70, v/v) | HPLC – MS/MS | 45 |
Plasma | Pack VP - ODS C18 column | phosphate buffer (pH7.0): ACN : methanol (91:0.1:9) | HPLC-UV at 274 nm | 46 |
Plasma | a C18 column | A gradient with 0.1% FA in water and 0.1% FA in methanol | HPLC – MS/MS | 47 |
Tablet | a C18 column | water: methanol (60:40 v/v) | HPLC-UV 270 nm | 48 |
Plasma | A Phenomonex C18 column | A queous solution of 15% ACN and 0.1% acetic acid | HPLC – MS/MS | 49 |
Tablet | A bondapak C18 | 0.02 M tri-sodium citrate and methanol (70:30 v/v) | HPLC-UV at 266 nm | 50 |
Tablet | A thermo BDS C18 column | A formic acid and methanol in the ratio of 50:50 | HPLC-UV at 264 nm | 51 |
Plasma | a C8 column | A gradient elution with 10 mM potassium phosphate, 3% ACN, and methanol | HPLC-UV at 272 nm | 52 |
Tablet | a Hypersil BDS, C18 column | o- phosphoric acid: methanol (70:30) | HPLC-UV at 220 nm | 53 |
Plasma | A Peerless Basic C18 column | 0.1% formic acid in water: methanol (15:85, v/v) | HPLC – MS/MS | 54 |
Tablet | a C18 column | methanol and water (89:11 v/v) | HPLC-UV at 272 nm | 55 |
Tablet | a Diamonsil Cl8 column | 0.025 mol ammonium acetate (pH 3.9 ± 0.1)-methanol (90:10). | HPLC-UV at 270 nm | 56 |
Plasma | a C18 column | A gradient elution with 10 mM acetate buffer (pH 6.5)- ACN | HPLC-UV at 265 nm | 57 |
Plasma | a Hypurity Advance C18 | ACN :0.1% FA (76:24, v/v) | HPLC – MS/MS | 58 |
Tablet | A LunaC18 | A gradient elution with 50mM ammonium acetate buffer (pH = 6.8) and methanol | HPLC-UV at 265 nm | 59 |
plasma | a Hypersil BDS, C18 column | 0.1 M ammonium acetate buffer in 0.5% acetic acid, v/v and methanol (40:60, v/v) | HPLC-UV at 270 nm | 60 |
Tablet | An YMC pack C8 column | buffer pH 3.5: methanol (90:10 v/v) | HPLC-UV at 265 nm | 61 |
Tablet | a Kromasil C18 analytical column | methanol: 10 mM phosphate buffer (pH 5.0) (70:30 v\v). | HPLC-UV at 254 nm | 62 |
Tablet | A Luna C18 | 0.1 % triethylamine (pH 5.11: ACN (70:30) | HPLC-UV at 245 nm | 63 |
Tablet | a Luna hydrophilic interaction column | ACN /10 mM ammonium formate (95:5, v/v) | HPLC – MS/MS | 64 |
Tablet | a C18 column | Agradient elution with 0.05 M Phosphate buffer (pH 6.2): ACN | HPLC-UV 260 nm | 65 |
Tablet | A Phenomenex Luna C18 column | ACN : methanol: water 30: 45: 25 (v/v/v) | HPLC-UV 258 nm | 66 |
Matrix | Stationary phase | Mobile phase | detector | Ref |
---|---|---|---|---|
Tablet | silica-gel 60 F254 plate | toluene/chloroform/methanol (1:6:3 v/v/v) | UV- 276 and 271 nm | 67 |
Tablet | silica-gel 60 F254 plate | Acetone: chloroform:methanol (4: 4: 2 v/v/v) | UV- 265nm | 68 |
Tablet | silica-gel 60 F254 plate | chloroform: methanol: toluene (8: 2: 2, v/v/v) | UV- 265nm | 69 |
Tablet | silica-gel 60 F254 plate | ethyl acetate, methanol, toluene and conc ammonia (38.7:19.4:38.7:3.2, v:v:v:v) | UV- 254nm | 70 |
Tablet | silica-gel 60 F254 plate | n-hexane: chloroform: methanol (1:7:2 v/v/v) | UV- 275 nm | 71 |
Conclusion
This literature review represents an up to date survey about all reported methods that have been developed for determination of the anticancer drug, lamivudine in its pure form, combined form with other drugs, combined form with degradation products, and in biological samples such as liquid chromatography, spectrophotometry, electrochemistry, etc...