Simultaneous quantification of four first line antitubercular drugs and metabolites in human plasma by hydrophilic interaction chromatography and tandem mass spectrometry

Sundell, Jesper; Bienvenu, Emile; Birgersson, Sofia; Äbelö, Angela; Ashton, Michael; Hoffmann, Kurt‐Jürgen

doi:10.1016/j.jchromb.2018.10.027

Cited by 20 publications

(20 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Novelty of the Developed Method. Compared with previous studies [10][11][12][13][14][15][16][17][18][19], HPLC column and mobile phase, together with gradient elution applied in this study, significantly improved the peak shapes. e total volume for sample analyzing was only 50 μL, which was much lower than the reported method.…”

Section: Application To Clinical Samplesmentioning

confidence: 55%

“…Some chromatography-based methods such as HPLC-ultraviolet detection, HPLC-fluorescence detection, and HPLC-tandem mass spectrometry (MS/MS) have been introduced. However, all of these methods have their own disadvantages, like a long time for chromatographic separation, complicated sample pretreatment, simultaneous quantification of only one to three drugs, and using homologues or other drugs as an internal standard [ 10 – 15 ]. Although some studies chose rifampicin-D3 as an isotope-labeled internal standard [ 16 – 18 ], our preexperiment indicated that rifampicin-D3 existed in the rifampicin standard, which might interfere with the quantification.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Development and Application of a LC-MS/MS Method for Simultaneous Quantification of Four First-Line Antituberculosis Drugs in Human Serum

Zheng

et al. 2020

Journal of Analytical Methods in Chemistry

View full text Add to dashboard Cite

A simple, rapid, and sensitive liquid chromatography (LC)/mass spectrometry (MS) method was established and validated for simultaneous quantitation of pyrazinamide, isoniazid, rifampicin, and ethambutol in human blood sample. Samples were pretreated by a single-step precipitation with acetonitrile. Chromatographic separation was achieved on XSelecT HSS T3 column by gradient elution with a total run time of 5.0 min. MS detection was performed by a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode with a positive electrospray ionization source. Isotope-labeled internal standard, especially rifampicin-D8, was applied to adjust for the loss during sample treatment. The established LC-MS/MS method showed a wide analytical range (pyrazinamide: 1.02∼60.0 μg/mL, isoniazid: 0.152∼10.0 μg/mL, rifampicin: 0.500∼30.0 μg/mL, and ethambutol: 0.0998∼5.99 μg/mL) and a good linearity (r > 0.99 for the four analytes) with acceptable accuracy and precision (90.15%∼104.62% and 94.00%∼104.02% for intra- and interaccuracy, respectively; RSD%: <12.46% and <6.43% for intra- and interprecision, respectively). It also showed excellent recoveries (79.24%∼94.16% for all analytes) and absence of significant matrix effect. This method was successfully applied to the quantification of four first-line antituberculosis (anti-TB) drugs, suggesting its suitability for therapeutic drug monitoring in the clinical practices.

show abstract

Section: Application To Clinical Samplesmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Development and Application of a LC-MS/MS Method for Simultaneous Quantification of Four First-Line Antituberculosis Drugs in Human Serum

Zheng

et al. 2020

Journal of Analytical Methods in Chemistry

View full text Add to dashboard Cite

show abstract

“…Plasma concentrations of INH, ACINH, and INA were quantified simultaneously by liquid chromatography with tandem mass spectrometry . In short, the method was validated according to US Food and Drug Administration (FDA) guidelines in the concentration range of 80–10,000 ng/mL for INH and INA and 40–5,000 ng/mL for ACINH.…”

Section: Methodsmentioning

confidence: 99%

Model‐Based Assessment of Variability in Isoniazid Pharmacokinetics and Metabolism in Patients Co‐Infected With Tuberculosis and HIV: Implications for a Novel Dosing Strategy

Sundell

Bienvenu

Janzén

et al. 2020

Clin Pharma and Therapeutics

Self Cite

View full text Add to dashboard Cite

Tuberculosis is the most common cause of death in HIV‐infected patients. Isoniazid is used as a first‐line drug to treat tuberculosis infection. However, variability in isoniazid pharmacokinetics can result in hepatotoxicity or treatment failure. Determination of clinical factors affecting isoniazid pharmacokinetics and metabolic pathways in HIV co‐infected patients is therefore critical. Plasma levels of isoniazid, acetyl‐isoniazid, and isonicotinic acid from 63 patients co‐infected with tuberculosis and HIV were analyzed by liquid chromatography with tandem mass spectrometry followed by nonlinear mixed‐effects modeling. Patients were genotyped to determine acetylator status. Patients were either on concomitant efavirenz‐based antiretroviral therapy or HIV treatment naïve. Clearances of isoniazid were 1.3‐fold and 2.3‐fold higher in intermediate and rapid acetylators, respectively, compared with slow acetylators. Patients on concomitant efavirenz‐based antiretroviral therapy had 64% and 80% higher population predicted clearances of acetyl‐isoniazid and isonicotinic acid, respectively, compared with patients who were HIV treatment naïve. Both sex and CD4 cell count affected the bioavailability of isoniazid. Variability in isoniazid exposure could be reduced by dose adaptions based on acetylator type and sex in addition to the currently used weight bands. A novel dosing strategy that has the potential to reduce isoniazid‐related toxicity and treatment failure is presented.

show abstract

“…Drug quantification. EMB concentrations in plasma were quantified using a liquid chromatographytandem mass spectrometry method described previously (32). Briefly, the method was validated over the range of 40 to 5,000 ng/ml for EMB.…”

Section: Methodsmentioning

confidence: 99%

Population Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIV

Sundell

Bienvenu

Birgersson

et al. 2020

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

This study aimed to characterize the population pharmacokinetics and pharmacogenetics of ethambutol in tuberculosis-HIV-coinfected adult patients. Ethambutol plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, in 63 patients receiving ethambutol as part of rifampin-based fixed-dose combination therapy for tuberculosis were analyzed using nonlinear mixed-effects modeling. A one-compartment disposition model with first-order elimination and four transit compartments prior to first-order absorption was found to adequately describe the concentration-time profiles of ethambutol in plasma. Body weight was implemented as an allometric function on the clearance and volume parameters. Estimates of oral clearance and volume of distribution were 77.4 liters/h and 76.2 liters, respectively. A G/A mutation with regard to CYP1A2 2159 G>A was associated with a 50% reduction in relative bioavailability. Simulations revealed that doses of 30 mg/kg of body weight and 50 mg/kg for G/G and G/A carriers, respectively, would result in clinically adequate exposure. The results presented here suggest that CYP1A2 polymorphism affects ethambutol exposure in this population and that current treatment guidelines may result in underexposure in patients coinfected with tuberculosis and HIV. Based on simulations, a dose increase from15 to 20 mg/kg to 30 mg/kg is suggested. However, the 50-mg/kg dose required to reach therapeutic exposure in G/A carriers may be inappropriate due to the dose-dependent toxicity of ethambutol. Additional studies are required to further investigate CYP450 polymorphism effects on ethambutol pharmacokinetics.

show abstract

Simultaneous quantification of four first line antitubercular drugs and metabolites in human plasma by hydrophilic interaction chromatography and tandem mass spectrometry

Cited by 20 publications

References 22 publications

Development and Application of a LC-MS/MS Method for Simultaneous Quantification of Four First-Line Antituberculosis Drugs in Human Serum

Development and Application of a LC-MS/MS Method for Simultaneous Quantification of Four First-Line Antituberculosis Drugs in Human Serum

Model‐Based Assessment of Variability in Isoniazid Pharmacokinetics and Metabolism in Patients Co‐Infected With Tuberculosis and HIV: Implications for a Novel Dosing Strategy

Population Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIV

Contact Info

Product

Resources

About