Liquid chromatography–tandem mass spectrometry assay for the quantitation of β-dihydroartemisinin in rat plasma

Xing, Jie; Yan, Hongxia; Wang, Ruili; Zhang, Lifeng; Zhang, Shuqiu

doi:10.1016/j.jchromb.2007.01.017

Cited by 18 publications

(9 citation statements)

References 13 publications

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“…Both electrospray (TIS) and atmospheric pressure chemical ionization (APCI) have been used previously for quantification of artemisinin derivatives in biological fluids [15,16,[19][20][21][22]. Both interfaces were evaluated on the basis of sensitivity and signal-to-noise ratios.…”

Section: Methods Developmentmentioning

confidence: 99%

A liquid chromatographic-tandem mass spectrometric method for determination of artesunate and its metabolite dihydroartemisinin in human plasma

Hanpithakpong

Kamanikom

Dondorp

et al. 2008

Journal of Chromatography B

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Section: Methods Developmentmentioning

confidence: 99%

A liquid chromatographic-tandem mass spectrometric method for determination of artesunate and its metabolite dihydroartemisinin in human plasma

Hanpithakpong

Kamanikom

Dondorp

et al. 2008

Journal of Chromatography B

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“…The presence of a peroxide bridge in the structure of DHA offers the advantage of using HPLC with reductive electrochemical detection [11][12][13]. HPLC with mass spectrometry (LC-MS) for the assay of DHA [14][15][16][17][18] was recently reported.…”

Section: Introductionmentioning

confidence: 99%

“…Xing et al [18] investigated the pharmacokinetic profile of b-DHA in rats after oral administration of 10 mg/ kg b-DHA and the mean values of C max and t max of DHA were 142.2 mg/l and 0.8 h, respectively. Simpson et al [19] studied the population pharmacokinetics of artesunate and DHA in malarial patients.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of dihydroartemisinin in Artekin tablets for single and repeated dosing in Chinese healthy volunteers

Hong

Liu

Huang

et al. 2008

Biopharm & Drug Disp

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Aim. To study the pharmacokinetics of dihydroartemisinin (DHA) in Artekin (compound dihydroartemisinin) tablets in Chinese healthy volunteers. Methods. Eighteen healthy volunteers (9 males, 9 females) received Artekin tablets for oral administration. The plasma samples of DHA were analysed by liquid-liquid extraction and determined by HPLC/ESI/MS. Results. The plasma DHA concentration-time curves of single dose and repeated doses of DHA were fitted to a two-compartment open model. The mean pharmacokinetic parameters of DHA in a single dose were: t(1/2(beta))=1.245 +/- 0.495 h, C(max)=243.6 +/- 56.15 microg/l, AUC(0 --> infinity)=450 +/- 69 h x microg/l, V(d)=5.75 +/- 2.2 l/kg and Cl=3.245 +/- 0.38 l/h/kg, while in repeated doses they were: t(1/2(beta))=1.085 +/- 0.298 h, AUC(0 --> infinity)=444.35 +/- 80.43 h x ng/ml, V(d)=4.62 +/- 1.128 ml/kg, Cl=3.0125 +/- 0.875 ml/h/kg, respectively. Conclusion. The study showed that DHA in Artekin was rapidly absorbed, distributed and eliminated in the healthy subjects. The pharmacokinetic properties of DHA in Artekin were not affected by gender in a single dose. While in repeated doses accumulation of DHA did not appear after repeated doses.

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“…Hybrid 2 reached a maximum concentration of 141 ± 56.8 ng/mL within 23 ± 5.77 min after a concentration of 20 mg/kg were administrated orally, whereas DHA reached a maximum concentration of 142.2 ± 21.1 ng/mL, in 48 ± 6 min after a dose of 10 mg/kg [20]. However, according to the recorded data DHA displayed a much longer half-life ip than hybrid 2 (25 min vs 3.9 min) [21].…”

Section: Discussionmentioning

confidence: 99%

“…However, according to the recorded data DHA displayed a much longer half-life ip than hybrid 2 (25 min vs 3.9 min) [21]. Subsequently DHA also displayed a higher AUC than hybrid 2 (8748 ± 2016 ng.min/mL vs 3463 ± 895 ng.min/mL) [20]. The oral volume of distribution of DHA was higher than that of hybrid 2 (353.5 ± 194.9 L/kg vs 34 ± 10.8 L/kg), whereas the clearance rate for hybrid 2 was 5 times that of DHA (6.1 L/min/kg vs 1.19 L/min/kg) [20].…”

Section: Discussionmentioning

confidence: 99%

Potent in vivo anti-malarial activity and representative snapshot pharmacokinetic evaluation of artemisinin-quinoline hybrids

Lombard

N’Da

et al. 2013

Malar J

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BackgroundBecause Plasmodium falciparum displays increase tolerance against the recommended artemisinin combination therapies (ACT), new classes of anti-malarial drugs are urgently required. Previously synthesized artemisinin-aminoquinoline hybrids were evaluated to ascertain whether the potent low nanomolar in vitro anti-plasmodial activity would carry over in vivo against Plasmodium vinckei. A snapshot pharmacokinetic analysis was carried out on one of the hybrids to obtain an indication of the pharmacokinetic properties of this class of anti-malarial drugs.MethodsIn vitro activity of hybrids 2 and 3 were determined against the 3D7 strain of P. falciparum. Plasmodium vinckei-infected mice were treated with hybrids 1 – 3 for four days at a dosage of 0.8 mg/kg, 2.5 mg/kg, 7.5 mg/kg or 15 mg/kg intraperitoneally (ip), or orally (per os) with 2.7 mg/kg, 8.3 mg/kg, 25 mg/kg or 50 mg/kg. Artesunate was used as reference drug. A snapshot oral and IV pharmacokinetic study was performed on hybrid 2.ResultsHybrids 1 – 3 displayed potent in vivo anti-malarial activity with ED50 of 1.1, 1.4 and <0.8 mg/kg by the ip route and 12, 16 and 13 mg/kg per os, respectively. Long-term monitoring of parasitaemia showed a complete cure of mice (without recrudescence) at 15 mg/kg via ip route and at 50 mg/kg by oral route for hybrid 1 and 2, whereas artesunate was only able to provide a complete cure at 30 mg/kg ip and 80 mg/kg per os.ConclusionsThese compounds provide a new class of desperately needed anti-malarial drug. Despite a short half-life and moderate oral bioavailability, this class of compounds was able to cure malaria in mice at very low dosages. The optimum linker length for anti-malarial activity was found to be a diaminoalkyl chain consisting of two carbon atoms either methylated or unmethylated.

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Liquid chromatography–tandem mass spectrometry assay for the quantitation of β-dihydroartemisinin in rat plasma

Cited by 18 publications

References 13 publications

A liquid chromatographic-tandem mass spectrometric method for determination of artesunate and its metabolite dihydroartemisinin in human plasma

A liquid chromatographic-tandem mass spectrometric method for determination of artesunate and its metabolite dihydroartemisinin in human plasma

Pharmacokinetics of dihydroartemisinin in Artekin tablets for single and repeated dosing in Chinese healthy volunteers

Potent in vivo anti-malarial activity and representative snapshot pharmacokinetic evaluation of artemisinin-quinoline hybrids

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