A high-performance liquid chromatography–tandem mass spectrometry method for the determination of artemether and dihydroartemisinin in human plasma

Hilhorst, Martijn; Hendriks, G.; Vries, Ronald de; Hillewaert, Vera; Verhaege, T; Merbel, Nico C. van de

doi:10.1016/j.jchromb.2014.06.006

Cited by 14 publications

(13 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results presented in Figure demonstrate that the response of ARM and DHA in even 2% hemolytic plasma was significantly improved after the pretreatment of hydrogen peroxide compared to that of untreated groups. Moreover, the addition of the 0.5% glacial acetic acid (pH 5.60) appears to provide an improved stabilizing effect for hydrogen peroxide as described in previous studies . At the same time, the response of LUM exhibited no significant change upon the addition of hydrogen peroxide and glacial acetic acid.…”

Section: Resultssupporting

confidence: 64%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 64%

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

View full text Add to dashboard Cite

show abstract

“…It was already reported that DHA in plasma is stable when stored at −80°C up to 6 months as well as after 5 freeze-thaw cycles [5]. When assaying pure plasma samples, we observed a matrix effect, leading to changes in the sensitivity and precision characteristics of the assay.…”

Section: Resultsmentioning

confidence: 54%

“…Among them, mainly high-performance liquid chromatography (HPLC) methods with mass spectrometric or electrochemical detection (HPLC-ECD) were developed for the measurement of AS or AM and DHA in human plasma including various sample preparation methods (e.g., solid-phase extraction, liquid-liquid extraction, and protein precipitation) [4][5][6][7]. Analytical methods were also developed for the simultaneous determination of several antimalarial drugs in human plasma since the artemisinin derivatives are routinely applied in combination with other antimalarial drugs [8,9].…”

Section: Introductionmentioning

confidence: 99%

Development of sensitive direct chemiluminescent enzyme immunoassay for the determination of dihydroartemisinin in plasma

et al. 2015

View full text Add to dashboard Cite

Despite significant progress in prevention and therapy, malaria is still one of the world's leading major diseases due to its high morbidity and mortality. Recommended treatments by the World Health Organization include the use of artemisinin and artemisinin derivative-based combination therapies. To allow efficient patient monitoring during antimalarial therapy without the use of expensive apparatus, we developed a sensitive direct chemiluminescent enzyme immunoassay for the determination of dihydroartemisinin in biological fluids. To produce specific antibodies against dihydroartemisinin (DHA), a synthetic DHA derivative was coupled to bovine serum albumin as the immunogen. In parallel, a new, rapid, and efficient procedure to covalently link glycoprotein to all amine-containing molecules has been established and the enzyme tracer was prepared by chemically coupling the DHA derivative in combination with SBP rather than the more commonly used HRP. It allowed us to develop, after optimization of the luminescent reagent, a sensitive and stable luminescent EIA, with a LLOQ of 90 pg mL(-1). This assay compares favorably with the most efficient HPLC methods previously reported with a LLOQ close to 1 ng mL(-1) and shows good precision and efficiency since recovery from human plasma spiked with DHA ranged between 91 and 103%, with coefficients of variation of <13%. To date, no immunoassay for DHA has been applied to plasma analysis and this EIA should be very useful in all clinical laboratories for rapid and cost-effective analysis.

show abstract

“…The authors postulated that the organic solvent releases the analytes from their binding plasma proteins and the iron from the iron II‐heme, enabling the iron to react with the analytes. It was reported that a solid‐phase extraction (SPE)–MS method could make artemisinin analogs relatively stable in hemolyzed plasma and quantify them (Hilhorst et al, ; Lindegardh et al, ; Naik, Murry, Kirsch, & Fleckenstein, ). Reactive cations in the native plasma sample were initially “shielded” from the drugs as a result of protein binding.…”

Section: Introductionmentioning

confidence: 99%

“…As reported, artemisinin analogs are relatively stable in hemolyzed plasma (i.e. in the presence of Fe 2+ products), but degrade rapidly when they come into contact with organic solvents during sample preparation (Hilhorst et al, 2014;Lindegardh et al, 2008). The authors postulated that the organic solvent releases the analytes from their binding plasma proteins and the iron from the iron II-heme, enabling the iron to react with the analytes.…”

mentioning

confidence: 95%

Quantitative determination of artemisinin in rat hemolyzed plasma by an HPLC–HRMS method

Wang

Sun

2019

Biomedical Chromatography

View full text Add to dashboard Cite

Iron present in hemolyzed plasma could cause the degradation of artemisinin by reductively cleaving the peroxide bridge of artemisinin during sample preparation, which is a significant technical challenge for artemisinin determination. In this paper, this issue was resolved by using sodium nitrite as methemoglobin‐forming agent to oxidize hemoglobin to methemoglobin in the presence of acetic acid and prevent the degradation of artemisinin in hemolyzed plasma during the sample preparation procedure. Then, a high‐performance liquid chromatography tandem high‐resolution mass spectrometry method was developed and validated for the determination of artemisinin in normal and hemolyzed plasma. The linear range was validated over the concentration range of 5–500 ng ml−1. The matrix effect and stability were also evaluated. This robust and sensitive assay was successfully applied to a pharmacokinetic study in rats after an oral administration of Artemisia annua L. extract.

show abstract

A high-performance liquid chromatography–tandem mass spectrometry method for the determination of artemether and dihydroartemisinin in human plasma

Cited by 14 publications

References 24 publications

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

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

Development of sensitive direct chemiluminescent enzyme immunoassay for the determination of dihydroartemisinin in plasma

Quantitative determination of artemisinin in rat hemolyzed plasma by an HPLC–HRMS method

Contact Info

Product

Resources

About