Research Article
TheValidationofaSimple,Robust,Stability-IndicatingRP-HPLC
MethodfortheSimultaneousDetectionofLamivudine,Tenofovir
DisoproxilFumarate,andDolutegravirSodiuminBulkMaterial
and Pharmaceutical Formulations
Omobolanle Ayoyinka Omoteso ,
1
MarnusMilne ,
2
andMariqueAucamp
1
1
School of Pharmacy, University of the Western Cape, Bellville, Cape Town, 7530, South Africa
2
School of Pharmacy, Sefako Makgatho Health Sciences University, Ga-Rankuwa, Pretoria 0208, South Africa
Correspondence should be addressed to Marique Aucamp; maucamp@uwc.ac.za
Received 20 September 2021; Revised 30 December 2021; Accepted 8 January 2022; Published 4 February 2022
Academic Editor: Mohamed Abdel-Rehim
Copyright © 2022 Omobolanle Ayoyinka Omoteso et al. is is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
An effective analytical method is requisite to ensure the accurate identification and quantification of drug(s), either in bulk
material or in complex matrices, which form part of finished pharmaceutical products. For the purpose of a pharmaceutical
formulation study, it became necessary to have a simple, yet robust and reproducible reversed-phase HPLC method for the
simultaneous detection and quantification of lamivudine (3TC), tenofovir disoproxil fumarate (TDF), and dolutegravir sodium
(DTG) in bulk form, complex polymeric matrices, and during drug release studies. A suitable method was developed using a
Kinetex
®
C
18
,250 × 4.6mmcolumnasstationaryphaseandamobilephaseconsistingof50:50v/vmethanolandwaterwith1mL
orthophosphoric acid, with a flow rate of 1.0 mL/min and column temperature maintained at 35
°
C. A detection wavelength of
260 nm and an injection volume of 10 μL were used. e method was validated according to the International Conference on
Harmonization (ICH) guideline Q2 (R
1
), and the parameters of linearity and range, accuracy, precision, specificity, limit of
detection (LOD), limit of quantification (LOQ), robustness, and stability were all determined. Acceptable correlation coefficients
for linearity (R
2
)of >0.998 for each of the three drugs were obtained. e LOD was quantified to be 56.31 μg/mL, 40.27 μg/mL, and
7.00 μg/mL for 3TC, TDF, and DTG, respectively, and the LOQ was quantified as 187.69 μg/mL, 134.22 μg/mL, and 22.5 μg/mL for
3TC, TDF, and DTG, respectively. In relation to all the determined validation parameters, this method proves to be suitable for the
accurate identification and quantification of the three ARVs, either alone or in combination, as well as when incorporated into
polymeric matrices. Furthermore, the method proves to be suitable to detect degradation of the compounds.
1.Introduction
Lamivudine (3TC) is a nucleoside analog reverse transcriptase
inhibitor (NRTI), used for the treatment of HIV-1, HIV-2,
and hepatitis B infection (Figure 1(a)) [1, 2]. Tenofovir dis-
oproxil fumarate (TDF) was the first nucleotide analog re-
verse transcriptase inhibitor (NtRTI) (Figure 1(b)), approved
for the treatment of HIV infection [3]. A combination of TDF
with other NRTIs and different classes of antiretroviral drugs
(ARVs) causes synergistic effects showing activity against all
subtypes of HIV-1 and certain strains of HIV-2 [4].
Dolutegravir (DTG) is a unique second-generation integrase
strand transfer inhibitor (INSTI) (Figure 1(c)), developed as a
result of the limitations of the first-generation INSTIs, which
includes potency, resistance by the virus, dosing frequency,
dosing weight, and drug genetic barrier [5–7]. It is effective
against numerous HIV-1 and HIV-2 clinical isolates [8]. e
2016 WHO Consolidated Guidelines recommended the
combination of the mentioned three ARVs as the first-line
regimen mainstay of HIV treatment. Currently, the combi-
nation of 3TC, TDF, and DTG is formulated as a fixed-dose
combination (FDC) oral tablet.
Hindawi
International Journal of Analytical Chemistry
Volume 2022, Article ID 3510277, 11 pages
https://doi.org/10.1155/2022/3510277