TY - JOUR

T1 - Optimization of HPLC–MS/MS method for determination of antimalarial adulterants in herbal products

AU - Mwankuna, Christopher J.

AU - Kiros, Feven

AU - Mariki, Eliapenda E.

AU - Mabiki, Faith P.

AU - Malebo, Hamisi M.

AU - Mdegela, Robinson H.

AU - Styrishave, Bjarne

N1 - Funding Information: We acknowledge the financial support of GRILI DANIDA project in carrying out this study. Publisher Copyright: © 2023, The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.

PY - 2023

Y1 - 2023

N2 - The use of herbal products is booming all over the world because of being believed as safer than conventional drugs and free of side effects. However, there are untrustworthy manufacturers who adulterate herbal products by adding conventional drugs which might eventually lead to microbial resistance and herb-to-drug interactions. There is a need to develop methods for detecting adulterants in herbal products. A high performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) method for simultaneous identification and determination of conventional antimalarials (chloroquine, quinine, sulfadoxine, pyrimethamine, mefloquine, lumefantrine, amodiaquine, artemisinin, dihydroartemisinin, artesunate and artemether) in herbal products was developed. Stable isotopically labelled compounds (artemether-d3, quindine-d3, and sulfadoxine-d3) were used as internal standards (ISs) for quantitative analysis. Extraction of analytes was performed using methanol: water: formic acid (90:10:0.1, v/v) and chromatographic separation was done in a gradient mode using mobile phase A: Ultrapure water containing 0.1% formic acid and 1 mM ammonium formate and mobile phase B: Acetonitrile/methanol (50:50) containing 0.1% formic acid and 1 mM ammonium formate. The calibration curves were linear (r2 ≥ 0.991) over the range of 0.001–0.3 µg mL−1 for all compounds. The limit of detection (LOD) ranged from 0.002 to 0.02 μg mL−1 while the limit of quantification (LOQ) ranged from 0.006 to 0.08 μg mL−1. Accuracy, expressed as recovery of spiked herbal products ranged from 52 to 128%. The precision, expressed as percent relative standard deviation (%RSD) at two concentration levels, ranged from 1.0 to 13.8%. The matrix effect expressed as the matrix factor (MF) ranged from 0.77 to 0.97. The developed method was used to identify and quantify conventional antimalarials in herbal product samples from Tanzania. Ten out of 50 herbal products were found to contain amodiaquine, sulfadoxine, pyrimethamine, mefloquine, dihydroartemisinin, artemether and lumefantrine. The developed method is considered a valuable tool for getting a better understanding of the adulteration of conventional antimalarials in herbal products. Graphical abstract: [Figure not available: see fulltext.]

AB - The use of herbal products is booming all over the world because of being believed as safer than conventional drugs and free of side effects. However, there are untrustworthy manufacturers who adulterate herbal products by adding conventional drugs which might eventually lead to microbial resistance and herb-to-drug interactions. There is a need to develop methods for detecting adulterants in herbal products. A high performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) method for simultaneous identification and determination of conventional antimalarials (chloroquine, quinine, sulfadoxine, pyrimethamine, mefloquine, lumefantrine, amodiaquine, artemisinin, dihydroartemisinin, artesunate and artemether) in herbal products was developed. Stable isotopically labelled compounds (artemether-d3, quindine-d3, and sulfadoxine-d3) were used as internal standards (ISs) for quantitative analysis. Extraction of analytes was performed using methanol: water: formic acid (90:10:0.1, v/v) and chromatographic separation was done in a gradient mode using mobile phase A: Ultrapure water containing 0.1% formic acid and 1 mM ammonium formate and mobile phase B: Acetonitrile/methanol (50:50) containing 0.1% formic acid and 1 mM ammonium formate. The calibration curves were linear (r2 ≥ 0.991) over the range of 0.001–0.3 µg mL−1 for all compounds. The limit of detection (LOD) ranged from 0.002 to 0.02 μg mL−1 while the limit of quantification (LOQ) ranged from 0.006 to 0.08 μg mL−1. Accuracy, expressed as recovery of spiked herbal products ranged from 52 to 128%. The precision, expressed as percent relative standard deviation (%RSD) at two concentration levels, ranged from 1.0 to 13.8%. The matrix effect expressed as the matrix factor (MF) ranged from 0.77 to 0.97. The developed method was used to identify and quantify conventional antimalarials in herbal product samples from Tanzania. Ten out of 50 herbal products were found to contain amodiaquine, sulfadoxine, pyrimethamine, mefloquine, dihydroartemisinin, artemether and lumefantrine. The developed method is considered a valuable tool for getting a better understanding of the adulteration of conventional antimalarials in herbal products. Graphical abstract: [Figure not available: see fulltext.]

KW - Adulteration

KW - Conventional drugs

KW - Herbal drugs

KW - Herbal products

U2 - 10.1007/s44211-022-00255-8

DO - 10.1007/s44211-022-00255-8

M3 - Journal article

C2 - 36633808

AN - SCOPUS:85146156893

VL - 39

SP - 407

EP - 416

JO - Analytical Sciences

JF - Analytical Sciences

SN - 0910-6340

ER -