An HPLC method with diode array detector for the simultaneous quantification of chloroquine and desethylchloroquine in plasma and whole blood samples from <i>Plasmodium vivax</i> patients in <scp>Vietnam</scp>, using quinine as an internal standard

Pham, Toi Van; Nguyen, Phuong Pham; Khanh, Tho Nguyen Duc; Thuy, Nhien Nguyen Thanh; Nha, Ca Nguyen Thuy; Pouplin, Thomas; Farrar, Jeremy; Thwaites, Guy; Tinh, Hien Tran

doi:10.1002/bmc.3657

Cited by 9 publications

(10 citation statements)

References 28 publications

(70 reference statements)

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“…Also a large sample volume for analysis requires more blood to be collected, which is a drawback if studies also involve young children [17,20–25,27]. Moreover, longer runtime for analysis makes these methods not suitable for high-throughput analysis of large sample batches from pharmacokinetic studies [21,23,28,29].…”

Section: Resultsmentioning

confidence: 99%

“…A recent publication with diode array detector used a more powerful sample extraction technique (e.g., SPE). However, this method still proved less sensitive (LLOQ of 10 ng/ml) using a large injection volume (50 μl) for improved sensitivity [29]. The introduction of mass spectrometric detection has become popular for its high sensitivity and selectivity that is useful for pharmacokinetic studies.…”

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confidence: 99%

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High Sensitivity Methods to Quantify Chloroquine and its Metabolite in Human Blood Samples Using LC–MS/MS

et al. 2019

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Aim: Chloroquine is an antimalarial drug used in the treatment of Plasmodium vivax malaria. Three methods to quantify chloroquine and its metabolite in blood matrices were developed and validated. Methodology & results: Different high-throughput extraction techniques were used to recover the drugs from whole blood (50 μl), plasma (100 μl) and dried blood spots (15 μl as punched discs) followed by quantification with LC–MS/MS. The intra- and inter-batch precisions were below 15%, and thus meet regulatory acceptance criteria. Conclusion: The developed methods demonstrated satisfactory validation performance with high sensitivity and selectivity. The assays used simple and easy to automate extraction techniques. All methods were reliable with robust performance and demonstrated to be suitable to implement into high-throughput routine analysis of clinical pharmacokinetic samples.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

High Sensitivity Methods to Quantify Chloroquine and its Metabolite in Human Blood Samples Using LC–MS/MS

et al. 2019

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“…For the sample preparation of CQ/HCQ different techniques were used including protein precipitation (PP) ( 6 , 33 , 34 , 40–45 ) and several extraction methodologies like liquid–liquid extraction (LLE) ( 5 , 38 , 39 , 46–52 ), solid-phase extraction (SPE) ( 37 , 38 , 53 , 54 ), 96-well plate LLE ( 55 , 56 ), microextraction techniques ( 57 ) as well as different sample collection techniques as volumetric absorptive microsampling (VAMS) ( 36 ) and dried blood spotting (DBS) ( 36–39 ).…”

Section: Methodsmentioning

confidence: 99%

“…HCQ was determined in blood samples via a VAMS device (tip) made from a proprietary hydrophilic polymer served as a sorbent of the SPE ( 36 ). Both plasma and whole blood samples were extracted on 96-fixed well plates by pretreatment of ACN, further treatment with PB pH 7.0 and ACN mixture, finally elution with ACN-formic acid (95: 5, v/v) mixture ( 54 ). An automated liquid handler platform used to process whole blood, plasma or punched discs of DBS samples spiked into 96-well plates as well as the removal of phospholipids, solid–liquid extraction to determine CQ and DCQ ( 37 ).…”

Section: Methodsmentioning

confidence: 99%

Liquid Chromatographic Methods for COVID-19 Drugs, Hydroxychloroquine and Chloroquine

Bilgin

Evcil

Yazgi

et al. 2020

Journal of Chromatographic Science

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COVID-19 has been a threat throughout the world since December 2019. In attempts to discover an urgent treatment regime for COVID-19, hydroxychloroquine (HCQ) and chloroquine (CQ) have been on solidarity clinical trial. However, many countries have pulled HCQ and CQ from their COVID-19 treatment regimens recently, some countries still continue using them for patients who have previously started HCQ and CQ and they may complete their course under the supervision of a doctor. HCQ and CQ are 4-aminoquinoline drugs and it is safe to use them for autoimmune diseases, rheumatoid arthritis, systemic lupus erythematosus and malaria as well. Determination of CQ, HCQ and their metabolites in biologic fluids and in pharmaceuticals has great importance, especially for pharmacokinetics, pharmacodynamics and epidemiological studies. In this review, liquid chromatographic methods developed in the last 10 years were summarized focusing on sample preparation and detection methods for HCQ and CQ determination in biological fluids and pharmaceutical preparations. It is hoped that this article could be helpful to facilitate the use of these drugs in clinical trials or drug research studies as it provides comprehensive information on the reported analytical methods.

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“…The concentrations of chloroquine and desethylchloroquine were measured using a reversed-phase HPLC system with fluorescence detection (Flexar, Perkin Elmer ™, Shelton, MA US) after liquid–liquid extraction as described by Alvan et al with minor modifications [21, 22]. Briefly, 80 µl of internal standard (quinine 2.5 µg/ml), 1 ml of 1 M sodium hydroxide, and 6 ml of diethyl ether were added to 500 µl of plasma sample and mixed by shaking for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Doses of chloroquine in the treatment of malaria by Plasmodium vivax in patients between 2 and 14 years of age from the Brazilian Amazon basin

Sena

Mello

Ferreira

et al. 2019

Malar J

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BackgroundA total dose of chloroquine of 25 mg/kg is recommended by the World Health Organization (WHO) to treat malaria by Plasmodium vivax. In several endemic areas, including the Brazilian Amazon basin, anti-malarial drugs are dispensed in small plastic bags at a dosing regimen based on age. This practice can lead to suboptimal dosing of the drug, which can impact treatment outcomes. The aim of the present study was to estimate the extent of sub-dosing of chloroquine in children and adolescents with vivax malaria using an age-based dose regimen, in addition to investigating the influence of age on the plasma concentrations of chloroquine and desethylchloroquine.MethodsA study of cases was conducted with male patients with a confirmed infection by P. vivax, ages 2 to 14 years, using a combined regimen of chloroquine and primaquine. Height, weight and body surface area were determined at admission on the study. The total dose of chloroquine administered was estimated based on the weight and on the body surface area of the study patients. Chloroquine and desethylchloroquine were measured on Day 7 in each patient included in the study by a high-performance liquid chromatographic method with fluorescence detection.ResultsA total of 81 patients were enrolled and completed the study. The median age was 9 years (2–14 years). All patients presented negative blood smears at 42 days follow-up. The total dose of chloroquine ranged from 13.1 to 38.1 mg/kg. The percentage of patients with a total dose of the drug below 25 mg/kg ranged from 29.4 to 63.6%. The total dose of chloroquine administered based on BSA ranged from 387 to 1079 mg/m2, increasing with age. Plasma chloroquine concentrations ranged from 107 to 420 ng/ml, increasing with age. For desethylchloroquine, the plasma concentrations ranged from 167 to 390 ng/ml, with similar values among age-groups.ConclusionThe data demonstrated the widespread exposure of children and adolescents to suboptimal doses of chloroquine in the endemic area investigated.

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An HPLC method with diode array detector for the simultaneous quantification of chloroquine and desethylchloroquine in plasma and whole blood samples from Plasmodium vivax patients in Vietnam, using quinine as an internal standard

Cited by 9 publications

References 28 publications

High Sensitivity Methods to Quantify Chloroquine and its Metabolite in Human Blood Samples Using LC–MS/MS

High Sensitivity Methods to Quantify Chloroquine and its Metabolite in Human Blood Samples Using LC–MS/MS

Liquid Chromatographic Methods for COVID-19 Drugs, Hydroxychloroquine and Chloroquine

Doses of chloroquine in the treatment of malaria by Plasmodium vivax in patients between 2 and 14 years of age from the Brazilian Amazon basin

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