LC-MS/MS method development and validation for simultaneous quantification of first-line HIV drugs and second-line TB drugs in rat plasma.
| dc.contributor.advisor | Govender, Thavendran. | |
| dc.contributor.advisor | Baijnath, Sooraj. | |
| dc.contributor.advisor | Naicker, Tricia. | |
| dc.contributor.advisor | Kruger, Hendrik Gerhardus. | |
| dc.contributor.author | Malinga, Thembeka Hlengiwe. | |
| dc.date.accessioned | 2020-04-03T16:35:22Z | |
| dc.date.available | 2020-04-03T16:35:22Z | |
| dc.date.created | 2018 | |
| dc.date.issued | 2018 | |
| dc.description | Masters Degree. University of KwaZulu-Natal, Durban. | en_US |
| dc.description.abstract | Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection continues to be a major public health concern, worldwide. HIV infection has increased the TB incidence over the past twenty years, making it hard to eliminate TB. At the same time, TB continues to be responsible for approximately 30% of deaths among HIV-infected individuals. Emtricitabine (FTC), efavirenz (EFV), and tenofovir (TFV) are constituents of a one-day-pill, AtriplaTM, which was approved in 2006 by the Food and Drug Administration (FDA). AtriplaTM is a triple combination anti-HIV drug that provides an efficient dosing plan. Streptomycin (STR), kanamycin (KAN), and ofloxacin (OFL) are second-line anti-TB drugs used to treat multidrug-resistant/ extensively drug-resistant tuberculosis (MDR/XDR-TB). The worldwide increase in the prevalence of anti-TB drugs resistance is of concern to researchers since it remains one of the most significant threats to the community. Co-prescription of anti-HIV and anti-TB drugs poses a challenge of drug-drug interactions, which causes adverse effects. Therapeutic drug monitoring (TDM) seems to be the tool for a solution to these problems since it personalizes doses thus reducing drug toxicity. LC-MS/MS methods with short run times are required to produce effective TDM studies. Therefore, this study aimed to evaluate the new Ascentis Express column technologies [pentafluorophenylpropyl (F5), octadecyl (C18), biphenyl, and reversed phase amide (RP-Amide)] and their applicability to the simultaneous quantification of current first-line anti-HIV treatment Atripla. It also aimed to develop, optimize and validate a liquid-chromatography tandem mass spectrometry (LC-MS/MS) methods for the simultaneous quantification of anti-HIV drugs (FTC, EFV, and TFV) and second-line anti-TB drugs (STR, KAN, and OFL) in rat plasma for the usage of TDM. The currently used HPLC columns have longer run times making them impractical in a point of care environment since the number of patients and diseases is globally increasing. There are also no or very few studies regarding the LC-MS/MS method of simultaneous HIV and TB drugs for HIV positive TB patients. The biphenyl column showed consistency and optimum performance with regard to the number of theoretical plates, resolution and peak asymmetry factor. It showed good separation and overall effectiveness. However, this does not rule out other columns for other purposes intended to be accomplished. The LC-MS/MS method developed for the simultaneous quantification of anti-HIV drugs and second-line anti-TB drugs was short to eleven minutes and met all the recommendations by the European Medicines Agency (EMA) guidelines for bioanalytical method validation. The new HPLC column matrices (F5, C18, biphenyl, and RP-Amide) offer various benefits such as the potential of saving solvents and short runtimes, essential in TDM studies. Therefore, the usage of the new HPLC column technologies iv will be beneficial in a point of care environment in terms of saving time and money. The LC-MS/MS method validated in this study can be used in clinical trials and in the simultaneous determination of the effective plasma concentrations of anti-TB and anti-HIV drugs, making it a strong candidate for TDM in a point of care setting. | en_US |
| dc.identifier.uri | https://researchspace.ukzn.ac.za/handle/10413/17571 | |
| dc.language.iso | en | en_US |
| dc.subject.other | LC-MS/MS. | en_US |
| dc.subject.other | Liquid chromatography-mass spectrometry (LC-MS/MS). | en_US |
| dc.subject.other | HIV-1 drug effects. | en_US |
| dc.subject.other | Drug resistance, Viral. | en_US |
| dc.subject.other | Antiretroviral agents--Pharmacology. | en_US |
| dc.subject.other | Tuberculosis, Multidrug-resistant therapy. | en_US |
| dc.subject.other | Tuberculosis drug therapy. | en_US |
| dc.title | LC-MS/MS method development and validation for simultaneous quantification of first-line HIV drugs and second-line TB drugs in rat plasma. | en_US |
| dc.type | Thesis | en_US |