Therapeutic drug monitoring by LC–MS–MS with special focus on anti-infective drugs

Müller, Daniel; Rentsch, Katharina

doi:10.1007/s00216-010-3986-z

Cited by 22 publications

(4 citation statements)

References 125 publications

(170 reference statements)

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“…Literature survey reveals that various UV-VIS spectroscopy [7][8] , HPTLC 9 , HPLC [10][11][12][13] , LC-MS [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] methods have been reported individually for the estimation of Dolutegravir and Lamivudine. None of the methods were reported for simultaneous estimation of Dolutegravir and Lamivudine.…”

Section: Fig1 Chemical Structures Of A) Dolutegravir B) Lamivudinementioning

confidence: 99%

Simultaneous Determination of Dolutegravir and Lamivudine in Human Plasma by LC-MS/MS

Bhadrua

Raob²,

Vidyadharab³

2021

Int J Life Sci Pharm Res

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A rapid, simple, sensitive and selective LC-MS/MS method has been developed and validated for quanti? cation of the Dolutegravir and Lamivudine in plasma samples. The analytical procedure involves a liquid-liquid extraction method using Emtricitabine as an internal standard (IS). The precision and accuracy data have to fulfill the requirements for quantification of the analytes in biological matrices to generate data for bioequivalence and bioavailability investigations. The chromatographic separation was achieved on a Hypurity Advance (4.6, 50 mm, 5µ) column using a mobile phase consisting of 0.1% formic acid buffer-acetonitrile (20:80, %v/v) at ? ow rate of 0.8 mL/min. The API-4000 LC-MS/MS was operated in the multiple-reaction monitoring mode using electrospray ionization. The total run time of analysis was 3 min and elution of Dolutegravir, Lamivudine and Emtricitabine (IS) occurred at 1.06, 1.84 and 0.92 min, respectively. A detailed validation of the method was performed as per the US Food and Drug Administration guidelines. The method was validated in terms of linearity, accuracy, precision, specificity, limit of detection and limit of quantitation. The standard curves found to be linear in the range of 0.10-30.0 ng/mL for Dolutegravir and 20.2-6026 ng/mL for Lamivudine, with a coef? cient of correlation of =0.99 for both the compounds. Dolutegravir and Lamivudine were found to be stable in a plasma stability studies, viz. bench-top, autosampler, re-injection, wet-extract and repeated freezethaw cycles. The coefficient of variation was =15% for intra-and inter-batch assays. The assay is suitable for pharmacokinetic study samples as demonstrated by its specificity, precision, accuracy, recovery, and stability characteristics.

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Section: Fig1 Chemical Structures Of A) Dolutegravir B) Lamivudinementioning

confidence: 99%

Simultaneous Determination of Dolutegravir and Lamivudine in Human Plasma by LC-MS/MS

Bhadrua

Raob²,

Vidyadharab³

2021

Int J Life Sci Pharm Res

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“…Liquid chromatography-tandem mass spectrometry (LC–MS/MS) is an alternative analytical technique used in the field of quantitative bioanalysis, including TDM. ( Müller and Rentsch, 2010 ; Adaway and Keevil, 2012 ). This technique provides a combination of high sensitivity, high throughput, wide dynamic range, multiplexing ability, and good reproducibility, and requires low sample volumes.…”

Section: Introductionmentioning

confidence: 99%

LC–MS/MS-based multiplex antibacterial platform for therapeutic drug monitoring in intensive care unit patients

et al. 2023

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Empirically prescribed standard dosing regimens of antibacterial agents may result in insufficient or excess plasma concentrations with persistently poor clinical outcomes, especially for patients in intensive care units (ICUs). Therapeutic drug monitoring (TDM) of antibacterial agents can guide dose adjustments to benefit patients. In this study, we developed a robust, sensitive, and simple liquid chromatography-tandem mass spectrometry (LC–MS/MS) platform for the quantification of 14 antibacterial and antifungal agents (beta-lactams piperacillin, cefoperazone, and meropenem; beta-lactamase inhibitors tazobactam and sulbactam; antifungal agents fluconazole, caspofungin, posaconazole, and voriconazole; and daptomycin, vancomycin, teicoplanin, linezolid, and tigecycline) that can be used for patients with severe infection. This assay requires only 100 µL of serum with rapid protein precipitation. Chromatographic analysis was performed using a Waters Acquity UPLC C8 column. Three stable isotope-labeled antibacterial agents and one analogue were used as internal standards. Calibration curves ranged from 0.1–100 μg/mL, 0.1–50 μg/mL, and 0.3–100 μg/mL for different drugs, and all correlation coefficients were greater than 0.9085. Intra- and inter-day imprecision and inaccuracy values were below 15%. After validation, this new method was successfully employed for TDM in routine practice.

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“…The existing methods for determination of DRV in patient samples are mostly liquid chromatography-coupled with tandem mass spectrometric detector (LC-MS/MS) [ 13 , 14 ]. These methods are time-consuming, have a limited throughput and require tedious extraction procedures that negatively affect the accuracy of the results [ 13 , 14 , 15 ]. Moreover, these instruments are very expensive to be available in most laboratories in third-world countries.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of Two Immunogens and Production of Polyclonal Antibody with High Affinity and Specificity for Darunavir

et al. 2020

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Darunavir (DRV) is a potent antiviral drug used for treatment of infections with human immunodeficiency virus (HIV). Effective and safe treatment with DRV requires its therapeutic drug monitoring (TDM) in patient’s plasma during therapy. To support TDM of DRV, a specific antibody with high affinity is required in order to develop a sensitive immunoassay for the accurate determination of DRV in plasma. In this study, two new and different immunogens were prepared and characterized. These immunogens were the DRV conjugates with keyhole limpet hemocyanin (KLH) protein. The first immunogen (DRV-KLH) was prepared by zero-length direct linking of DRV via its aromatic amino group with the tyrosine amino acid residues of KLH by diazotization/coupling reaction. The second immunogen (G-DRV-KLH) was prepared by conjugation of the N-glutaryl derivative of DRV (G-DRV) with KLH. The 5-carbon atoms-spacing G-DRV hapten was synthesized by reaction of DRV via its aromatic amino group with glutaric anhydride. The reaction was monitored by HPLC and the chemical structure of G-DRV was confirmed by mass, 1H-NMR, and 13C-NMR spectroscopic techniques. The hapten (G-DRV) was linked to the KLH protein by water-soluble 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) coupling procedure. The pertinence of the coupling reactions of haptens to protein was confirmed, and the immunogens were characterized by ultraviolet (UV) spectrophotometry. Both DRV-KLH and G-DRV-KLH were used for the immunization of animals and the animal’s antiserum that showed the highest affinity was selected. The collected antiserum (polyclonal antibody) had very high affinity to DRV (IC50 value = 0.2 ng mL−1; defining IC50 as the DRV concentration that can inhibit antibody binding by 50% of its maximum binding) and high specificity to DRV among other drugs used in the combination therapy with DRV. Cumulative results from direct and competitive enzyme-linked immunosorbent assay (ELISA) using this polyclonal antibody proved that the immunogens were highly antigenic and elicited a specific polyclonal antibody. The produced polyclonal antibody is valuable for the development of highly sensitive and selective immunoassays for TDM of DRV.

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Therapeutic drug monitoring by LC–MS–MS with special focus on anti-infective drugs

Cited by 22 publications

References 125 publications

Simultaneous Determination of Dolutegravir and Lamivudine in Human Plasma by LC-MS/MS

Simultaneous Determination of Dolutegravir and Lamivudine in Human Plasma by LC-MS/MS

LC–MS/MS-based multiplex antibacterial platform for therapeutic drug monitoring in intensive care unit patients

Preparation and Characterization of Two Immunogens and Production of Polyclonal Antibody with High Affinity and Specificity for Darunavir

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