Development, validation and clinical application of a LC-MS/MS method for the simultaneous quantification of hydroxychloroquine and its active metabolites in human whole blood

Soichot, Marion; Mégarbane, Bruno; Houzé, Pascal; Chevillard, L; Fonsart, Julien; Baud, Frédéric J.; Laprévôte, Olivier; Bourgogne, Emmanuel

doi:10.1016/j.jpba.2014.07.009

Cited by 33 publications

(23 citation statements)

References 27 publications

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“…In the present study, the mean steady-state HCQ concentration was 1336 ± 621 ng/ml in 37 SLE patients treated with HCQ dose ranging from 200 to 600 mg/day, which suggests that our LLOQ is clinically relevant for TDM of HCQ. The LLOQ for DHCQ and DCQ (25 ng/ml) is similar with recent LLOQ reported with LC–MS/MS [21]. Additionally, the mean steady-state DHCQ and DCQ concentration was 1037 ± 721 ng/ml and 115 ± 54 ng/ml, respectively.…”

Section: Resultssupporting

confidence: 85%

Development and validation of a clinical HPLC method for the quantification of hydroxychloroquine and its metabolites in whole blood

Qu¹,

Noé

Breaud³

et al. 2015

Future Sci. OA

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Background:Therapeutic drug monitoring for hydroxychloroquine (HCQ) has been suggested to assess nonadherence and optimize treatment efficacy in systemic lupus erythematosus patients.Materials & methods:After protein precipitation, HCQ and its metabolites, desethylhydroxychloroquine and desethylchloroquine were separated on a phenyl column and monitored by fluorescence detection. The method was linear from 50 to 4000 ng/ml for HCQ. The intra-day and inter-day precision of HCQ, desethylhydroxychloroquine and desethylchloroquine ranged from 4.3 to 10.3%. LLOQ was 50 ng/ml for HCQ.Conclusion:The method is very practical and was applied to routinely monitor the steady state whole blood exposure of HCQ and its metabolites in systemic lupus erythematosus patients. It well correlated with our LC–MS/MS and another HPLC method.

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Section: Resultssupporting

confidence: 85%

Development and validation of a clinical HPLC method for the quantification of hydroxychloroquine and its metabolites in whole blood

Qu¹,

Noé

Breaud³

et al. 2015

Future Sci. OA

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“…Analytical solutions exist for monitoring (hydroxy)chloroquine drug concentrations. [31][32][33] Regarding efficacy, interpretation of such TDM data is difficult because of the lack of data on target concentrations, timing of measurement, and drug adjustment strategy in the context of COVID-19 treatment. Avoiding toxic exposure is even more important considering the long half-life of (hydroxy) chloroquine; hence, monitoring (hydroxy)chloroquine concentrations is suggested for this purpose.…”

Section: Recommendationsmentioning

confidence: 99%

Pharmacologic Treatment of Transplant Recipients Infected With SARS-CoV-2: Considerations Regarding Therapeutic Drug Monitoring and Drug–Drug Interactions

Elens

Langman

Hesselink

et al. 2020

Therapeutic Drug Monitoring

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Background: COVID-19 is a novel infectious disease caused by the severe acute respiratory distress (SARS)-coronavirus-2 (SARS-CoV-2). Several therapeutic options are currently emerging but none with universal consensus or proven efficacy. Solid organ transplant recipients are perceived to be at increased risk of severe COVID-19 because of their immunosuppressed conditions due to chronic use of immunosuppressive drugs (ISDs). It is therefore likely that solid organ transplant recipients will be treated with these experimental antivirals. Methods: This article is not intended to provide a systematic literature review on investigational treatments tested against COVID-19; rather, the authors aim to provide recommendations for therapeutic drug monitoring of ISDs in transplant recipients infected with SARS-CoV-2 based on a review of existing data in the literature. Results: Management of drug-drug interactions between investigational anti-SARS-CoV-2 drugs and immunosuppressants is a complex task for the clinician. Adequate immunosuppression is necessary to prevent graft rejection while, if critically ill, the patient may benefit from pharmacotherapeutic interventions directed at limiting SARS-CoV-2 viral replication. Maintaining ISD concentrations within the desired therapeutic range requires a highly individualized approach that is complicated by the pandemic context and lack of hindsight. Conclusions: With this article, the authors inform the clinician about the potential interactions of experimental COVID-19 treatments with ISDs used in transplantation. Recommendations regarding therapeutic drug monitoring and dose adjustments in the context of COVID-19 are provided.

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“…Although LC–MS/MS methods have been developed and validated for quantitation of HCQ [17–20], limitations in these methods still preclude their implementation in PK studies involving mice. Soichot et al has provided a method for the quantitation of HCQ with all three of its major metabolites in whole blood, however with a LLOQ of 25 ng/mL[19]. Hong-Wei Fan et al later developed a more sensitive method of HCQ quantitation using plasma with a LLOQ of 0.2 ng/mL, but did not explore the method’s potential for metabolite analysis nor HCQ analysis from blood or tissue [20].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC–ESI–MS/MS: An application for pharmacokinetic studies

Chhonker

Sleightholm

et al. 2018

Journal of Chromatography B

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Hydroxychloroquine (HCQ) has been shown to disrupt autophagy and sensitize cancer cells to radiation and chemotherapeutic agents. However, the optimal delivery method, dose, and tumor concentrations required for these effects are not known. This is in part due to a lack of sensitive and reproducible analytical methods for HCQ quantitation in small animals. As such, we developed and validated a selective and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues. The chromatographic separation and detection of analytes were achieved on a reversed phase Thermo Aquasil C (50×4.6mm, 3μ) column, with gradient elution using 0.2% formic acid and 0.1% formic acid in methanol as mobile phase at a flow rate of 0.5mL/min. Simple protein precipitation was utilized for extraction of analytes from the desired matrix. Analytes were separated and quantitated using MS/MS with an electrospray ionization source in positive multiple reaction monitoring (MRM) mode. The MS/MS response was linear over the concentration range from 1 to 2000ng/mL for all analytes with a correlation coefficient (R) of 0.998 or better. The within- and between-day precision (relative standard deviation, % RSD) and accuracy were within the acceptable limits per FDA guidelines. The validated method was successfully applied to a preclinical pharmacokinetic mouse study involving low volume blood and tissue samples for hydroxychloroquine and metabolites.

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Development, validation and clinical application of a LC-MS/MS method for the simultaneous quantification of hydroxychloroquine and its active metabolites in human whole blood

Cited by 33 publications

References 27 publications

Development and validation of a clinical HPLC method for the quantification of hydroxychloroquine and its metabolites in whole blood

Development and validation of a clinical HPLC method for the quantification of hydroxychloroquine and its metabolites in whole blood

Pharmacologic Treatment of Transplant Recipients Infected With SARS-CoV-2: Considerations Regarding Therapeutic Drug Monitoring and Drug–Drug Interactions

Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC–ESI–MS/MS: An application for pharmacokinetic studies

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