Therapeutic drug monitoring using saliva as matrix: an opportunity for linezolid, but challenge for moxifloxacin

Elsen, Simone H.J. van den; Akkerman, Onno W.; Jongedijk, Erwin M; Wessels, Mireille; Ghimire, Samiksha; Werf, Tjip S van der; Touw, Daan; Bolhuis, Mathieu S.; Alffenaar, Jan‐Willem C.

doi:10.1183/13993003.01903-2019

Cited by 15 publications

(22 citation statements)

References 13 publications

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“…0.05 mg/L). 16 However, the established PK/PD target for linezolid is an AUC 0-24 /MIC ratio >119 6 and limited sampling strategies could be developed for saliva as has been done in the past for plasma samples 28 to use minimal sampling timepoints for AUC prediction. Hence, the need for trough sampling and detection below 3.0 mg/L may not be necessary with such sampling strategies.…”

Section: Discussionmentioning

confidence: 99%

“…15 To increase the feasibility of TDM during TB treatment, alternative sampling matrices have been explored, such as dried blood spots, saliva and urine. [16][17][18][19] These methods are non-invasive and allow ambulatory sampling. Due to the small sample volume, dried blood spot analysis requires sensitive LC-MS/MS equipment, which is rarely available.…”

Section: Introductionmentioning

confidence: 99%

“…Saliva is an attractive matrix for clinical application as linezolid has a substantial penetration into saliva with a saliva/plasma ratio of 0.76-0.97 observed for linezolid saliva concentrations of up to about 15 mg/L. 16,20 Clinical studies have reported a good correlation between plasma and saliva concentrations based on full concentration-time curves using LC-MS/MS to measure linezolid in saliva. 16,20 Although HPLC-UV is easier to perform than LC-MS/MS, it still requires skilled laboratory scientists, which does not facilitate access to TDM in local healthcare settings.…”

Section: Introductionmentioning

confidence: 99%

“…16,20 Clinical studies have reported a good correlation between plasma and saliva concentrations based on full concentration-time curves using LC-MS/MS to measure linezolid in saliva. 16,20 Although HPLC-UV is easier to perform than LC-MS/MS, it still requires skilled laboratory scientists, which does not facilitate access to TDM in local healthcare settings. More promising for programmatic implementation of TDM is the use of a mobile UV spectrophotometer.…”

Section: Introductionmentioning

confidence: 99%

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Saliva-based linezolid monitoring on a mobile UV spectrophotometer

Kim

Ruiter

Jongedijk

et al. 2021

Journal of Antimicrobial Chemotherapy

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Background In TB, therapeutic drug monitoring (TDM) is recommended for linezolid; however, implementation is challenging in endemic settings. Non-invasive saliva sampling using a mobile assay would increase the feasibility of TDM. Objectives To validate a linezolid saliva assay using a mobile UV spectrophotometer. Methods The saliva assay was developed using NanoPhotometer NP80® and linezolid concentrations were quantified using second-order derivative spectroscopy. Sample preparation involved liquid–liquid extraction of saliva, using saturated sodium chloride and ethyl acetate at 1:1:3 (v/v/v). The assay was validated for accuracy, precision, selectivity, specificity, carry-over, matrix effect, stability and filters. Acceptance criteria were bias and coefficient of variation (CV) <15% for quality control (QC) samples and <20% for the lower limit of quantification (LLOQ). Results Linezolid concentrations correlated with the amplitude between 250 and 270 nm on the second-order derivative spectra. The linezolid calibration curve was linear over the range of 3.0 to 25 mg/L (R2 = 0.99) and the LLOQ was 3.0 mg/L. Accuracy and precision were demonstrated with bias of −7.5% to 2.7% and CV ≤5.6%. The assay met the criteria for selectivity, matrix effect, carry-over, stability (tested up to 3 days) and use of filters (0.22 μM Millex®-GV and Millex®-GP). Specificity was tested with potential co-medications. Interferences from pyrazinamide, levofloxacin, moxifloxacin, rifampicin, abacavir, acetaminophen and trimethoprim were noted; however, with minimal clinical implications on linezolid dosing. Conclusions We validated a UV spectrophotometric assay using non-invasive saliva sampling for linezolid. The next step is to demonstrate clinical feasibility and value to facilitate programmatic implementation of TDM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Saliva-based linezolid monitoring on a mobile UV spectrophotometer

Kim

Ruiter

Jongedijk

et al. 2021

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

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“…Precision dosing strategy for linezolid should be guided by PK/PD target attainment using point-of-care TDM together with active TB drug safety monitoring and management (7). The use of simple, noninvasive point-of-care tests (e.g., testing of saliva samples) could facilitate TDM implementation in resource-limited, high-TB-burden settings, where this is most needed (8,9).…”

mentioning

confidence: 99%