Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies.
Identifieur interne : 000C16 ( Main/Exploration ); précédent : 000C15; suivant : 000C17Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies.
Auteurs : Yashpal S. Chhonker [États-Unis] ; Richard L. Sleightholm [États-Unis] ; Jing Li [États-Unis] ; David Oupick [États-Unis] ; Daryl J. Murry [États-Unis]Source :
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [ 1873-376X ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Chromatographie en phase liquide (), Foie (), Foie (métabolisme), Hydroxychloroquine (), Hydroxychloroquine (analyse), Hydroxychloroquine (pharmacocinétique), Hydroxychloroquine (sang), Limite de détection, Modèles linéaires, Mâle, Poumon (), Poumon (métabolisme), Reproductibilité des résultats, Répartition dans les tissus, Souris, Souris de lignée BALB C, Spectrométrie de masse ESI (), Spectrométrie de masse en tandem ().
- MESH :
- analyse : Hydroxychloroquine.
- métabolisme : Foie, Poumon.
- pharmacocinétique : Hydroxychloroquine.
- sang : Hydroxychloroquine.
- Animaux, Chromatographie en phase liquide, Foie, Hydroxychloroquine, Limite de détection, Modèles linéaires, Mâle, Poumon, Reproductibilité des résultats, Répartition dans les tissus, Souris, Souris de lignée BALB C, Spectrométrie de masse ESI, Spectrométrie de masse en tandem.
English descriptors
- KwdEn :
- Animals, Chromatography, Liquid (methods), Hydroxychloroquine (analysis), Hydroxychloroquine (blood), Hydroxychloroquine (chemistry), Hydroxychloroquine (pharmacokinetics), Limit of Detection, Linear Models, Liver (chemistry), Liver (metabolism), Lung (chemistry), Lung (metabolism), Male, Mice, Mice, Inbred BALB C, Reproducibility of Results, Spectrometry, Mass, Electrospray Ionization (methods), Tandem Mass Spectrometry (methods), Tissue Distribution.
- MESH :
- chemical , analysis : Hydroxychloroquine.
- chemical , blood : Hydroxychloroquine.
- chemical , chemistry : Hydroxychloroquine.
- chemistry : Liver, Lung.
- metabolism : Liver, Lung.
- methods : Chromatography, Liquid, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry.
- chemical , pharmacokinetics : Hydroxychloroquine.
- Animals, Limit of Detection, Linear Models, Male, Mice, Mice, Inbred BALB C, Reproducibility of Results, Tissue Distribution.
Abstract
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 C18 (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 (R2) 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.
DOI: 10.1016/j.jchromb.2017.11.026
PubMed: 29207305
Affiliations:
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Chhonker</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE 68198, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE 68198</wicri:regionArea><placeName><region type="state">Nebraska</region></placeName></affiliation></author><author><name sortKey="Sleightholm, Richard L" sort="Sleightholm, Richard L" uniqKey="Sleightholm R" first="Richard L" last="Sleightholm">Richard L. Sleightholm</name><affiliation wicri:level="2"><nlm:affiliation>Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198</wicri:regionArea><placeName><region type="state">Nebraska</region></placeName></affiliation></author><author><name sortKey="Li, Jing" sort="Li, Jing" uniqKey="Li J" first="Jing" last="Li">Jing Li</name><affiliation wicri:level="2"><nlm:affiliation>Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198</wicri:regionArea><placeName><region type="state">Nebraska</region></placeName></affiliation></author><author><name sortKey="Oupick, David" sort="Oupick, David" uniqKey="Oupick D" first="David" last="Oupick">David Oupick</name><affiliation wicri:level="2"><nlm:affiliation>Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198</wicri:regionArea><placeName><region type="state">Nebraska</region></placeName></affiliation></author><author><name sortKey="Murry, Daryl J" sort="Murry, Daryl J" uniqKey="Murry D" first="Daryl J" last="Murry">Daryl J. Murry</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE 68198, United States; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: dj.murry@unmc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE 68198, United States; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198</wicri:regionArea><placeName><region type="state">Nebraska</region></placeName></affiliation></author></analytic><series><title level="j">Journal of chromatography. 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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<sub>18</sub> (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<sup>2</sup>) 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.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Nebraska</li></region></list><tree><country name="États-Unis"><region name="Nebraska"><name sortKey="Chhonker, Yashpal S" sort="Chhonker, Yashpal S" uniqKey="Chhonker Y" first="Yashpal S" last="Chhonker">Yashpal S. Chhonker</name></region><name sortKey="Li, Jing" sort="Li, Jing" uniqKey="Li J" first="Jing" last="Li">Jing Li</name><name sortKey="Murry, Daryl J" sort="Murry, Daryl J" uniqKey="Murry D" first="Daryl J" last="Murry">Daryl J. Murry</name><name sortKey="Oupick, David" sort="Oupick, David" uniqKey="Oupick D" first="David" last="Oupick">David Oupick</name><name sortKey="Sleightholm, Richard L" sort="Sleightholm, Richard L" uniqKey="Sleightholm R" first="Richard L" last="Sleightholm">Richard L. Sleightholm</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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