Bio-analytical Assay Methods used in Therapeutic Drug Monitoring of Antiretroviral Drugs-A Review

Background: Several clinical trials, as well as observational statistics, have exhibited that the advantages of antiretroviral [ARV] treatment for humans with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome HIV/AIDS exceed their risks. Therapeutic drug monitoring [TDM] plays a key role in optimization of ARV therapy. Determination of ARV's in plasma, blood cells, and other biological matrices frequently requires separation techniques capable of high effectiveness, specific selectivity and high sensitivity. High-performance liquid chromatography [HPLC] coupled with ultraviolet [UV], Photodiode array detectors [PDA], Mass spectrophotometer [MS] detectors etc. are the important quantitative techniques used for the estimation of pharmaceuticals in biological samples. Objective: This review article is aimed to give an extensive outline of different bio-analytical techniques which have been reported for direct quantitation of ARV's. This article aimed to establish an efficient role played by the TDM in the optimum therapeutic outcome of the ARV treatment. It also focused on establishing the prominent role played by the separation techniques like HPLC and UPLC along with the detectors like UV and Mass in TDM. Methods: TDM is based on the principle that for certain drugs, a close relationship exists between the plasma level of the drug and its clinical effect. TDM is of no value if the relationship does not exist. The analytical methodology employed in TDM should: 1) distinguish similar compounds; 2) be sensitive and precise and 3) is easy to use Results: This review highlights the advancement of the chromatographic techniques beginning from the HPLC-UV to the more advanced technique like UPLC-MS/MS. TDM is essential to ensure adherence, observe viral resistance and to personalize ARV dose regimens. It is observed that the analytical methods like immunoassays and liquid chromatography with detectors like UV, PDA, Florescent, MS, MS/MS and Ultra performance liquid chromatography (UPLC)-MS/MS have immensely contributed to the clinical outcome of the ARV therapy. Assay methods are not only helping physicians in limiting the side effects and drug interactions but also assisting in monitoring patient's compliance. Conclusion: The present review revealed that HPLC has been the most widely used system irrespective of the availability of more sensitive chromatographic technique like UPLC.VRAID (ex DIPUC

Assessment of interindividual variability of plasma concentrations after administrazion of high doses of intravenous amoxicillin or cloxacillin in critically ill patients.

International audienceThe aim of the present retrospective observational clinical study was to assess the interindividual pharmacokinetic variability of plasma concentrations of amoxicillin or cloxacillin administered in high doses intravenously in critically ill patients, related to renal function or administration method.Four hundred and two plasma concentrations were measured at steady-state with a high performance liquid chromatography technique in 162 patients treated with 100 - 300 mg/kg/day of intravenous amoxicillin or cloxacillin.For both drugs and administration methods, plasma concentrations were significantly higher for patients with creatinine clearance below 60 ml/min, even though doses were adapted for renal impairment. the correlations calculated between plasma concentrations and creatinine level, creatinine clearance or doses were all low. There were fewer outlying drug concentrations in patients receiving continuous rather than intermittent regimens.Our results are in favor of adapting dosages of these beta-lactam antibiotics based on plasma concentrations, especially in cases of renal impairment