Applying Dried Blood Spot Sampling with LCMS Quantification in The Clinical Development Phase of Tasquinimod

Svensson, Leif; Sennbro, Carl Johan; Svanström, Camilla; Hansson, G.P.

doi:10.4155/bio.14.259

Cited by 6 publications

(6 citation statements)

References 23 publications

(36 reference statements)

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“…Hence, red blood cells might have a slight diluting effect on PZQ concentrations, depending on the blood hematocrit [ 26 ]. For example, tasquinimod, an anticancer drug characterized by a very high plasma binding (>98%), revealed a blood:plasma ratio of 66% [ 44 , 45 ]. This phenomenon was also observed in a study comparing DBS and plasma sampling with piperacillin and tazobactam in infants with DBS:plasma ratios between 50 and 60% [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Study of Praziquantel Enantiomers and Its Main Metabolite R-trans-4-OH-PZQ in Plasma, Blood and Dried Blood Spots in Opisthorchis viverrini-Infected Patients

et al. 2016

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BackgroundPraziquantel (PZQ) is the treatment of choice for infections with the liver fluke Opisthorchis viverrini, a major health problem in Southeast Asia. However, pharmacokinetic (PK) studies investigating the disposition of PZQ enantiomers (R- and S-PZQ) and its main metabolite, R-trans-4-OH-PZQ, in diseased patients are lacking. The implementation of a dried blood spot (DBS) sampling technique would ease the performance of PK studies in remote areas without clinical facilities. The aim of the present study is to provide data on the disposition of PZQ enantiomers and R-trans-4-OH-PZQ in opisthorchiasis patients and to validate the use of DBS compared to plasma and blood sampling.Methodology/Principal FindingsPZQ was administered to nine O. viverrini-infected patients at 3 oral doses of 25 mg/kg in 4 h intervals. Plasma, blood and DBS were simultaneously collected at selected time points from 0 to 24 h post-treatment. PK parameters were determined using non-compartmental analysis. Drug concentrations and areas under the curve (AUC0–24h) measured in the 3 matrices were compared using Bland-Altman analysis. We observed plasma AUC0–24hs of 1.1, 9.0 and 188.7 μg/ml*h and half-lives of 1.1, 3.3 and 6.4 h for R-PZQ, S-PZQ and R-trans-4-OH, respectively. Maximal plasma concentrations (Cmax) of 0.2, 0.9 and 13.9 μg/ml for R-PZQ, S-PQZ and R-trans-4-OH peaked at 7 h for PZQ enantiomers and at 8.7 h for the metabolite. Individual drug concentration measurements and patient AUC0–24hs displayed ratios of blood or DBS versus plasma between 79–94% for R- and S-PZQ, and between 108–122% for R-trans-4-OH.Conclusions/SignificancePharmacodynamic (PD) in vitro studies on PZQ enantiomers and R-trans-4-OH-PZQ are necessary to be able to correlate PK parameters with efficacy. DBS appears to be a valid alternative to conventional venous sampling for PK studies in PZQ-treated patients.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Study of Praziquantel Enantiomers and Its Main Metabolite R-trans-4-OH-PZQ in Plasma, Blood and Dried Blood Spots in Opisthorchis viverrini-Infected Patients

et al. 2016

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“…This detection, as stated by the authors, provided only qualitative measurement for MPH measurement and the method reported an LOD value with no LOQ. Thus, considering the rarity of validated bioanalytical assays using DBS in clinical settings, we thoroughly investigated probable variables in DBS validation assay [37,38,39] and that this assay can be successfully applied for PK, PK/PD or bioequivalence studies of MPH in both adults or adolescent patient populations.…”

Section: Graphical Abstractmentioning

confidence: 99%

Novel and Rapid LC–MS/MS Method for Quantitative Analysis of Methylphenidate in Dried Blood Spots

et al. 2018

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“…Bestetik, aipatutako zuloaren bidezko analisi kuantitatiboa aurrera eraman nahi bada, analitoen banaketa homogeneoa gertatu behar da odol-tantan zehar, edozein puntutan zuloa hartuta ere beti analitoen kontzentrazio berdina egoteko. Horren ondorioz, analitoen banaketak faktore batzuekiko duen mendekotasuna kontuan hartu behar da, besteak beste odol mota (zainetakoa edo kapilarra) [13,14], euskarri mota [10,15], hematokritoa (odolaren dentsitatearekin lotuta) [3,13,14,[16][17][18] eta odoltantaren bolumena [19,20].…”

Section: Odol Tanta Lehorraren Fidagarritasunaren Azterketa Farmakoen...unclassified

“…Kontuan hartu behar da zenbat eta handiagoa izan bolumena, orduan eta erantzun baxuagoa edukiko dela analitoen diluzioagatik nahiz eta berreskurapena hobetu. Modu berean, bolumen txikiegia erabiltzean posible da disoluzioa asetzea eta berreskurapen baxua lortzea [5,7,16,20]. Horretan guztian oinarrituta 100-500 µL-ko tartea aztertu da.…”

Section: Erauzlearen Bolumenaren Hautatzeaunclassified

Odol Tanta Lehorraren fidagarritasunaren azterketa farmakoen analisi kuantitatiborako UHPLC-PDA-FLDren bidez

Uribe

González²,

Alonso³

2016

EKAIA

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Lan honetan Odol Tanta Lehorraren (OTLa) laginketa-teknikaren fidagarritasuna ikertu da farmakoen analisirako fotodiodo- eta fluoreszentzia-detektagailuei akoplatutako bereizmen oso altuko likido-kromatografiaren (UHPLC-PDA-FLD) bidez. OTLak, odol-tanta bat kotoi-paperezko euskarri batean jartzean eta lehortzen uztean datzan teknikak, azken urteotan erabileraren handipen garrantzitsua antzeman du bioanalisian. OTLak ohiko odol-analisiekiko hainbat abantaila erakutsi arren, analisi kuantitatiboaren ikuspuntutik hainbat faktorerekiko mendekotasuna duela antzeman da. Ikerketa honetan faktore batzuek (hematokritoa, odol-bolumena eta laginketa-puntua) farmakoen determinazioan duten eragina aztertu da, horretarako amilorida, propranolola eta valsartan farmakoak eredu gisa erabiliz. Emaitzetan oinarrituta, zuloaren kokapenak eta hematokritoak analisien zehaztasunean eta doitasunean eragina dutela ondorioztatu da, teknika honen aplikazio kuantitatiboa mugatuz. Bestalde, analitoen sakabanaketa odol-tantan zehar analitoen propietate fisiko-kimikoen mendekoa dela ikusi da, metodo analitikoaren garapenean analito bakoitzaren sakabanaketa aztertu behar dela ondorioztatuz.

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Applying Dried Blood Spot Sampling with LCMS Quantification in The Clinical Development Phase of Tasquinimod

Abstract: The method described here is suitable for bioanalysis of tasquinimod in whole blood from humans in clinical studies.

Cited by 6 publications

References 23 publications

Pharmacokinetic Study of Praziquantel Enantiomers and Its Main Metabolite R-trans-4-OH-PZQ in Plasma, Blood and Dried Blood Spots in Opisthorchis viverrini-Infected Patients

Pharmacokinetic Study of Praziquantel Enantiomers and Its Main Metabolite R-trans-4-OH-PZQ in Plasma, Blood and Dried Blood Spots in Opisthorchis viverrini-Infected Patients

Novel and Rapid LC–MS/MS Method for Quantitative Analysis of Methylphenidate in Dried Blood Spots

Odol Tanta Lehorraren fidagarritasunaren azterketa farmakoen analisi kuantitatiborako UHPLC-PDA-FLDren bidez

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