New approach to rifampicin stability and first-line anti-tubercular drug pharmacokinetics by UPLC-MS/MS

Karaźniewicz−Łada, Marta; Kosicka-Noworzyń, Katarzyna; Rao, Prakruti; Modi, Nisha; Xie, Yingda L.; Heysell, Scott K; Kagan, Leonid

doi:10.1016/j.jpba.2023.115650

Cited by 6 publications

(7 citation statements)

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“…Analysis of the tested compounds using a validated UPLC-MS/MS method in urine samples from five patients showed that the samples contained RIF-Q and 3-F-RIF ( Table 5 ), suggesting that RIF may be degraded during sample preparation or storage. The concentration of RIF-Q was in the range of 0.71–2.62 µg/mL (average 1.9 ± 0.8 µg/mL), and comprised 3.6–13.2% of the sum of RIF and RIF-Q (almost twice than reported in plasma [ 37 ]). Similarly, 3-F-RIF peak was detected in all samples ( Figure 1 ), and the concentration of the compound was an average of 1.3 ± 1.3 µg/mL ( Table 5 ), while it was previously below LLOQ in plasma [ 37 ].…”

Section: Discussionmentioning

confidence: 92%

“…The concentration of RIF-Q was in the range of 0.71–2.62 µg/mL (average 1.9 ± 0.8 µg/mL), and comprised 3.6–13.2% of the sum of RIF and RIF-Q (almost twice than reported in plasma [ 37 ]). Similarly, 3-F-RIF peak was detected in all samples ( Figure 1 ), and the concentration of the compound was an average of 1.3 ± 1.3 µg/mL ( Table 5 ), while it was previously below LLOQ in plasma [ 37 ]. Given the potential conversion between RIF and RIF-Q and the variations in pH during urine storage, additional research is needed to explore the degradation pathway of RIF.…”

Section: Discussionmentioning

confidence: 92%

“…While working solutions were stable for 1 month at −20 °C [ 37 ], an 8-month assessment revealed RIF-Q, 3-F-RIF, 25-D-RIF, and INH instability. Short-term stability data indicated metabolite stability within 24 h when frozen, but 30 days showed significant decomposition of RIF-Q and 3-F-RIF.…”

Section: Discussionmentioning

confidence: 99%

“…It is noteworthy that mild alkaline environments also foster RIF-Q generation [ 36 ]. In plasma, INH, PZA, RIF, and 25-D-RIF stability were discussed earlier [ 37 ]. However, there is rare information about the stability in different pH ranges, particularly in urine.…”

Section: Introductionmentioning

confidence: 99%

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Development and Validation of a UPLC-MS/MS Method for Therapeutic Drug Monitoring, Pharmacokinetic and Stability Studies of First-Line Antituberculosis Drugs in Urine

Abouzid,

Kosicka-Noworzyń,

Karaźniewicz-Łada

et al. 2024

Molecules

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Tuberculosis (TB) remains one of the leading global causes of mortality. Several methods have been established to detect anti-TB agents in human plasma and serum. However, there is a notable absence of studies analyzing TB drugs in urine. Thus, our objective was to validate a method for quantifying first-line anti-TB agents: isoniazid (INH), pyrazinamide (PZA), ethambutol (ETH), and rifampicin (RIF), along with its metabolite 25-desacetylrifampicin, and degradation products: rifampicin quinone and 3-formyl-rifampicin in 10 µL of urine. Chromatographic separation was achieved using a Kinetex Polar C18 analytical column with gradient elution (5 mM ammonium acetate and acetonitrile with 0.1% formic acid). Mass spectrometry detection was carried out using a triple-quadrupole tandem mass spectrometer operating in positive ion mode. The lower limit of quantification (LLOQ) was 0.5 µg/mL for INH, PZA, ETH, and RIF, and 0.1 µg/mL for RIF’s metabolites and degradation products. The method was validated following FDA guidance criteria and successfully applied to the analysis of the studied compounds in urine of TB patients. Additionally, we conducted a stability study of the anti-TB agents under various pH and temperature conditions to mimic the urine collection process in different settings (peripheral clinics or central laboratories).

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development and Validation of a UPLC-MS/MS Method for Therapeutic Drug Monitoring, Pharmacokinetic and Stability Studies of First-Line Antituberculosis Drugs in Urine

Abouzid,

Kosicka-Noworzyń,

Karaźniewicz-Łada

et al. 2024

Molecules

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“…Bioanalysis of rifampicin may require an adjuvant (ascorbic acid) to prevent degradation, as evidenced by many authors. 15–18 Adequate storage conditions (e.g. −80°C) and timely processing of plasma samples are recommended.…”

Section: Discussionmentioning

confidence: 99%

Ten-year results of an international external quality control programme for measurement of anti-tuberculosis drug concentrations

Stemkens,

Mouhdad,

Franssen

et al. 2024

Journal of Antimicrobial Chemotherapy

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Objectives Participation in an external (interlaboratory) quality control (QC) programme is an essential part of quality assurance as it provides laboratories with valuable insights into their analytical performance. We describe the 10 year results of an international QC programme for the measurement of anti-tuberculosis (TB) drugs. Methods Each year, two rounds were organized in which serum (or plasma) samples, spiked with known concentrations of anti-TB drugs, were provided to participating laboratories for analysis. Reported measurements within 80%–120% of weighed-in concentrations were considered accurate. Mixed model linear regression was performed to assess the effect of the measured drug, concentration level, analytical technique and performing laboratory on the absolute inaccuracy. Results By 2022, 31 laboratories had participated in the QC programme and 13 anti-TB drugs and metabolites were included. In total 1407 measurements were reported. First-line TB drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) represented 58% of all measurements. Overall, 83.2% of 1407 measurements were accurate, and the median absolute inaccuracy was 7.3% (IQR, 3.3%–15.1%). The absolute inaccuracy was related to the measured anti-TB drug and to the performing laboratory, but not to the concentration level or to the analytical technique used. The median absolute inaccuracies of rifampicin and isoniazid were relatively high (10.2% and 10.9%, respectively). Conclusions The 10 year results of this external QC programme illustrate the need for continuous external QC for the measurement of anti-TB drugs for research and patient care purposes, because one in six measurements was inaccurate. Participation in the programme alerts laboratories to previously undetected analytical problems.

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Urinary drug metabolite profiling of tuberculosis treatment failure using proton nuclear magnetic resonance

Opperman,

Mason,

van der Westhuizen

et al. 2024

Journal of Pharmaceutical and Biomedical Analysis

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New approach to rifampicin stability and first-line anti-tubercular drug pharmacokinetics by UPLC-MS/MS

Cited by 6 publications

References 32 publications

Development and Validation of a UPLC-MS/MS Method for Therapeutic Drug Monitoring, Pharmacokinetic and Stability Studies of First-Line Antituberculosis Drugs in Urine

Development and Validation of a UPLC-MS/MS Method for Therapeutic Drug Monitoring, Pharmacokinetic and Stability Studies of First-Line Antituberculosis Drugs in Urine

Ten-year results of an international external quality control programme for measurement of anti-tuberculosis drug concentrations

Urinary drug metabolite profiling of tuberculosis treatment failure using proton nuclear magnetic resonance

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