Quantitative Analysis of Artemether and its Metabolite Dihydroartemisinin in Human Plasma by LC with Tandem Mass Spectrometry

Shi, Bin; Yu, Yunqiu; Li, Zhongdong; Zhang, Li; Zhong, Yan; Su, Shengmin; Liang, Shipiao

doi:10.1365/s10337-006-0064-y

Cited by 23 publications

(24 citation statements)

References 12 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%

Section: Introductionmentioning

confidence: 99%

“…Studies employing mass spectrometry (MS) to quantify these drugs have used electrospray ionization for lumefantrine 9,15,16 and atmospheric pressure chemical ionization for artemether. 17,18 Quantitation was the main focus of these studies, therefore product ions and dissociation routes of these drugs by tandem mass spectrometry were not thoughtfully evaluated.The determination of the dissociation pathways of these main antimalarial drugs should benefit their monitoring by MS techniques in pharmaceutical products and biological fluids and the proper identification of artemether and lumefantrine derivatives and analogues. Herein we described our results of an investigation via electrospray ionization and tandem mass spectrometry performed in a high resolution and high accuracy hybrid quadrupole timeof-flight mass spectrometer of the dissociation chemistry of the protonated or cationized molecules of artemether and lumefantrine.…”

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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%

Section: Artemethermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

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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Current literature in mass spectrometry

2007

J. Mass Spectrom.

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1 REVIEWS Akashi S. Structural and functional characterization of biological macromolecules by mass spectrometry (Japanese, English Abstract). Yakugaku Zasshi 2006; 126: 915. Alder L, Greulich K, Kempe G, Vieth B. Residue analysis of 500 high priority pesticides: Better by GC-MS or LC-MS/MS? Mass Spectrom Rev 2006; 25: 838. Chaurand P, Norris JL, Cornett DS, Mobley JA, Caprioli RM. New developments in profiling and imaging of proteins from tissue sections by MALDI mass spectrometry. J Proteome Res 2006; 5: 2889. Downard KM. Ions of the interactome: The role of MS in the study of protein interactions in proteomics and structural biology. Proteomics 2006; 6: 5374. Englander SW. Hydrogen exchange and mass spectrometry: A historical perspective. -residue analytical methods using LC-tandem MS for the determination of pharmaceuticals in environmental and wastewater samples: A review. Anal Bioanal Chem 2006; 386: 941. Haslam SM, North SJ, Dell A. Mass spectrometric analysis of N-and O-glycosylation of tissues and cells. Curr Opin Struct Biol 2006; 16: 584. Kuster M, De Alda ML, Barcelo D. Analysis of pesticides in water by liquid chromatography-tandem mass spectrometric techniques. Mass Spectrom Rev 2006; 25: 900. Lacorte S, Fernandez-Albaz AR. Time of flight mass spectrometry applied to the liquid chromatographic analysis of pesticides in water and food. Mass Spectrom Rev 2006; 25: 866. Leitner A, Lindner W. Chemistry meets proteomics: The use of chemical tagging reactions for MS-based proteomics. Proteomics 2006; 6: 5418. Michel R, Castner DG. Advances in time-of-flight secondary ion mass spectrometry analysis of protein films. Surf Interface Anal 2006; 38: 1386. Nash DG, Baer T, Johnston MV. Aerosol mass spectrometry: An introductory review. Int J Mass Spectrom 2006; 258: 2. Nibbering NMM. Four decades of joy in mass spectrometry. Mass Spectrom Rev 2006; 25: 962. Niessen WMA, Manini P, Andreoli R. Matrix effects in quantitative pesticide analysis using liquid chromatography-mass spectrometry. Mass Spectrom Rev 2006; 25: 881. Pico Y, Font G, Ruiz MJ, Fernandez M. Control of pesticide residues by liquid chromatography-mass spectrometry to ensure food safety. Mass Spectrom Rev 2006; 25: 917. Qian WJ, Jacobs JM, Liu T, Camp DG, Smith RD. Advances and challenges in liquid chromatography-mass spectrometry-based proteomics profiling for clinical applications. Mol Cell Proteomics 2006; 5: 1727. Villagrasa M, De Alda ML, Barcelo D. Environmental analysis of fluorinated alkyl substances by liquid chromatography-(tandem) mass spectrometry: A review. Anal Bioanal Chem 2006; 386: 953.

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A sensitive, high‐throughput, and ecofriendly method for the determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin by supercritical fluid chromatography and tandem mass spectrometry

Yang

Gao

Hou

et al. 2018

J of Separation Science

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A quick and sensitive supercritical fluid chromatography with tandem mass spectrometry method for the simultaneous determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin in rat plasma was developed and validated. The chromatographic separation was performed on an ACQUITY UPC ™ BEH 2-EP column within 2.5 min by gradient elution using compressed CO and methanol containing 2 mM ammonium acetate as the mobile phases. Detection was achieved by multiple reaction monitoring using electrospray ionization in the positive ionization mode. For sample preparation, 50 μL of the sample was processed by modified high-throughput, one-step protein precipitation using hydrogen peroxide as a stabilizer to protect the endoperoxide-containing artemisinin derivatives from degradation. The calibration curves were linear over the concentration range of 2.0-1000 ng/mL for both artemether and dihydroartemisinin, and 1.0-5000 ng/mL for lumefantrine. The values of selectivity, lower limit of quantification, linearity, accuracy, precision, matrix effects, stability, and recovery met the acceptable range according to the Food and Drug Administration guidelines. The developed method enables high resolution and speed as well as low cost, low solvent consumption, and short time and was successfully applied to pharmacokinetic studies through the intravenous administration of an artemether-lumefantrine lipid emulsion in rats.

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Quantitative Analysis of Artemether and its Metabolite Dihydroartemisinin in Human Plasma by LC with Tandem Mass Spectrometry

Cited by 23 publications

References 12 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

Current literature in mass spectrometry

A sensitive, high‐throughput, and ecofriendly method for the determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin by supercritical fluid chromatography and tandem mass spectrometry

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