A high‐performance liquid chromatography/tandem mass spectrometry method for the determination of artemisinin in rat plasma

Xing, Jie; Yan, Hongxia; Zhang, Shuqiu; Ren, Guolian; Gao, Yanhui

doi:10.1002/rcm.2467

Cited by 46 publications

(35 citation statements)

References 15 publications

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“…Artemether Previous reports on the MS detection of the artemether molecule 18,19 have reported on the failure to observe the intact protonated molecule and used therefore only fragments and secondary dissociations for its quantitation. of a neutral LiOCH 3 forms the product ion of m/z 221, which dissociates in turn by the loss of acetone to form the ion of m/z 163.…”

Section: Resultsmentioning

confidence: 99%

“…Previous reports on the MS detection of the artemether molecule 18,19 have reported on the failure to observe the intact protonated molecule and used therefore only fragments and secondary dissociations for its quantitation. 18 and Xing et al 19 also found an ion of m/z 163 for the ESI-MS of artemether and proposed a distinct chemical structure for it based on a different mechanistic rationalization.…”

Section: Artemethermentioning

confidence: 99%

“…18 and Xing et al 19 also found an ion of m/z 163 for the ESI-MS of artemether and proposed a distinct chemical structure for it based on a different mechanistic rationalization. We however favor the routes outlined in Scheme 2.…”

Section: Artemethermentioning

confidence: 99%

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Electrospray ionization tandem mass spectrometry of the two main antimalarial drugs: artemether and lumefantrine

Santos¹,

Alves²,

Eberlin³

et al. 2012

J. Braz. Chem. Soc.

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Ionização por electrospray no modo de íons positivos, e espectrometria de massas de alta resolução e exatidão, e em tandem, realizadas em espectrômetro de massas híbrido quadrupolo e tempo de vôo, foram utilizadas para investigar a dissociação química das moléculas intactas dos dois antimaláricos mais amplamente utilizados: artemeter e lumefantrina. As rotas de dissociação das formas cationizadas e protonadas foram claramente estabelecidas via determinações de massas de alta resolução e distribuição isotópica. Os resultados obtidos podem auxiliar a monitorização e a quantificação de artemeter e lumefantrina por LC-MS/MS, assim como de novos derivados ou outros fármacos antimaláricos estruturalmente relacionados.Electrospray ionization in the positive ion mode and high resolution and high accuracy tandem mass spectrometry performed in a hybrid quadrupole time-of-flight mass spectrometer were used to investigate the dissociation chemistry of the intact molecules of two most widely used antimalarial drugs: artemether and lumefantrine. The dissociation pathways of their cationized and protonated forms were rationalized based on high accuracy mass measurements and isotopic distributions. The obtained results should benefit LC-MS/MS monitoring and quantitation by mass spectrometry of the artemether and lumefantrine molecules, as well as of new derivatives or other structurally related antimalarial drugs. Keywords: artemether, lumefantrine, ion dissociation, tandem mass spectrometry, ESI-MS/MS IntroductionArtemether-lumefantrine is a drug association currently of wide use for malaria treatment. The registered fixed dose combination is commercialized in tablets that contain 20 mg of artemether and 120 mg of lumefantrine. 1 The World Health Organization (WHO) recommends this association as first line therapy for falciparum malaria in endemic areas, mainly when cases of resistance against traditional drugs are reported. 2 Artemether (Scheme 1) is a semisynthetic derivative of artemisinin, a natural product of the Chinese herb Artemisia annua, 3 whereas lumefantrine (Scheme 1) is a synthetic racemic fluorene derivative originally named benflumetol. 4 Counterfeiting or drugs with substandard antimalarial doses are however major problems of worldwide occurrence that dramatically affects the efficacy of malarial treatment. Ineffective or poor quality drugs is of great concern since their use may contribute to the development of plasmodium resistance in malaria endemic areas, due to the exposition to subtherapeutic doses. 5,6 The development of useful and reliable methods for the identification of antimalarials is therefore essential to evaluate the quality of the antimalarial pharmaceutical preparations. Electrospray Ionization Tandem Mass Spectrometry of the Two Main Antimalarial Drugs J. Braz. Chem. Soc. 66 Chromatographic methods for the analysis of artemether and lumefantrine have been reported, focusing on the quantitation of these drugs in pharmaceutical products 7 or biological matrices. 8,9 HPLC with UV detection ...

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Section: Resultsmentioning

confidence: 99%

Section: Artemethermentioning

confidence: 99%

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Electrospray ionization tandem mass spectrometry of the two main antimalarial drugs: artemether and lumefantrine

Santos¹,

Alves²,

Eberlin³

et al. 2012

J. Braz. Chem. Soc.

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“…[14][15][16][17][18][19][20] Currently, the suitable method for quantification of these compounds in plasma is liquid chromatography coupled with mass spectrometry detection (LC-Ms or LC-MS/MS) with quantification limits of approximately 1 ng/mL using only 50-μL plasma sample volumes. [21][22][23][24][25] However, some of the problems encountered the latter bioanalytical methods include lack of appropriate stable isotope-labeled AS and DHA internal standards, in addition to expensive solid phase extraction cartridges that most commonly used for extraction of AS and DHA from biological samples.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

Matar

Awad

Elamin

2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Artesunate (AS) in combination with sulfadoxine/pyrimethamine (SP) is the first-line therapy for management of uncomplicated Plasmodium falciparum malaria in Sudan. The objective of this study was to assess the potential impact of SP on the pharmacokinetics of AS and its active metabolite, dihydroartemisinin (DHA), in healthy adults. A single-dose, randomized, open-label, crossover study design with a washout period of three weeks was performed with 16 volunteers. After oral administration of AS alone or in combination with SP, T max values of AS and DHA were significantly prolonged in the combination group (P 0.05). However, there was no significant effect on the other pharmacokinetic parameters (P 0.05). The t 1/2 values of AS and DHA were significantly higher in females than in males (P 0.05). The present findings suggest that co-administration of SP with AS has no clinically relevant impact on the pharmacokinetics of AS or DHA in healthy persons.

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“…Some other recent methods for the assay of these drugs alone or in combination with other antimalarials have also been reported [24][25][26][27][28]. However, these methods still had some limitations related to the chromatography and detection in terms of resolution, time-consuming, and requiring prolonged derivatization.…”

Section: Introductionmentioning

confidence: 99%

Highly sensitive liquid chromatographic analysis of artemisinin and its derivatives after pre-column derivatization with 4-carboxyl-2,6-dinitrobenzene diazonium ion

Adegoke¹,

Xiang²,

Chen³

2012

Acta Chromatographica

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Summary.A highly sensitive and reproducible isocratic liquid chromatographic method has been developed for the analysis of artemisinin and its three commonly used derivatives (artesunate, dihydroartemisinin, and artemether). The method involves a precolumn derivatization reaction with 4-carboxyl-2,6-dinitrobenzene diazonium ion to produce azo adducts that are UV-active. The critical parameters for the derivatization such as temperature, reaction time, and reagent concentrations were studied and optimized. The chromatographic separations were carried out on a C-18 column with mobile phase consisting of acetonitrile-0.1% acetic acid (60:40) at a flow rate of 1 mL min −1 . UV detection was set at 254 nm. Dynamic linear calibration range was obtained at concentrations of artemisinins ranging from 0.26 to 1.44 μg mL −1 . The low limits of detections of artemisinin, artesunate, dihydroartemisinin, and artemether were found to be 0.091, 0.0125, 0.0489, and 0.0128 ng μL −1 , respectively. The developed methods were precise (RSD <3%) and accurate (% error <5%). The developed methods may find application in dosage form analysis and pharmacokinetic studies.

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A high‐performance liquid chromatography/tandem mass spectrometry method for the determination of artemisinin in rat plasma

Cited by 46 publications

References 15 publications

Electrospray ionization tandem mass spectrometry of the two main antimalarial drugs: artemether and lumefantrine

Electrospray ionization tandem mass spectrometry of the two main antimalarial drugs: artemether and lumefantrine

Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

Highly sensitive liquid chromatographic analysis of artemisinin and its derivatives after pre-column derivatization with 4-carboxyl-2,6-dinitrobenzene diazonium ion

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