A Simple and Efficient HPLC Method for Benznidazole Dosage in Human Breast Milk

Marson, María Elena; Padró, Juan M.; Reta, Mario; Altcheh, Jaime; García-Bournissen, Facundo; Mastrantonio, Guido

doi:10.1097/ftd.0b013e31828f5214

Cited by 10 publications

(9 citation statements)

References 34 publications

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“…However, the LODs and LOQs obtained here were calculated by a more rigorous procedure than that used in Ref. . On the other hand, the R % (78%) was higher in this work, with a better precision (1.5%) than that reported in Ref.…”

Section: Resultsmentioning

confidence: 50%

“…Thus, a comparison with the figures of merit obtained in the present paper is not possible. For BNZ, the obtained results were compared with the ones obtained by Marson et al . They used a tandem microfiltration system after protein precipitation and HPLC–UV analysis, with no preconcentration step.…”

Section: Resultsmentioning

confidence: 99%

“…The methodology is quick, reproducible, and selective but, although is sensitive, the detection limit (0.75 μg/mL) resulted to be similar to others previously published in the literature due to a serious matrix effect (90% of signal suppression), which affected the ESI‐MS/MS detector. Up to our knowledge, the only published paper about determination of BNZ in human breast milk is that corresponding to Marsón et al . They developed a simple and fast RP‐HPLC–UV method with a sample pretreatment that involves acid protein precipitation followed by tandem microfiltration.…”

Section: Introductionmentioning

confidence: 99%

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Development of an ionic‐liquid‐based dispersive liquid–liquid microextraction method for the determination of antichagasic drugs in human breast milk: Optimization by central composite design

Padró

Vidal

Echevarria

et al. 2015

J of Separation Science

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Chagas disease constitutes a major public health problem in Latin America. Human breast milk is a biological sample of great importance for the analysis of therapeutic drugs, as unwanted exposure through breast milk could result in pharmacological effects in the nursing infant. Thus, the goal of breast milk drug analysis is to inquire to which extent a neonate may be exposed to a drug during lactation. In this work, we developed an analytical technique to quantify benznidazole and nifurtimox (the two antichagasic drugs currently available for medical treatment) in human breast milk, with a simple sample pretreatment followed by an ionic‐liquid‐based dispersive liquid–liquid microextraction combined with high‐performance liquid chromatography and UV detection. For this technique, the ionic liquid 1‐octyl‐3‐methylimidazolium hexafluorophosphate has been used as the “extraction solvent.” A central composite design was used to find the optimum values for the significant variables affecting the extraction process: volume of ionic liquid, volume of dispersant solvent, ionic strength, and pH. At the optimum working conditions, the average recoveries were 77.5 and 89.7%, the limits of detection were 0.06 and 0.09 μg/mL and the interday reproducibilities were 6.25 and 5.77% for benznidazole and nifurtimox, respectively. The proposed methodology can be considered sensitive, simple, robust, accurate, and green.

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Section: Resultsmentioning

confidence: 50%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of an ionic‐liquid‐based dispersive liquid–liquid microextraction method for the determination of antichagasic drugs in human breast milk: Optimization by central composite design

Padró

Vidal

Echevarria

et al. 2015

J of Separation Science

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“…High performance liquid chromatography was used to determine BNZ concentration in plasma and milk, as previously described 18 19. The limit of detection (LOD) and limit of quantitation (LOQ) for plasma were 0.14 and 0.32 mg/L, respectively.…”

Section: Population and Methodsmentioning

confidence: 99%

Limited infant exposure to benznidazole through breast milk during maternal treatment for Chagas disease

et al. 2014

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“…However, several methods have been described for BNZ quantification in animal and human plasma, urine, and milk (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). To evaluate BNZ biodistribution, a bioanalytical method was developed to determine its quantification in mouse tissues, including spleen, brain, heart, colon, liver, lung, and kidney.…”

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confidence: 99%

Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice

Perin

Silva

Fonseca

et al. 2017

Antimicrob Agents Chemother

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Specific chemotherapy using benznidazole (BNZ) for Chagas disease during the chronic stage is controversial due to its limited efficacy and toxic effects. Although BNZ has been used to treat Chagas disease since the 1970s, few studies about the biodistribution of this drug exist. In this study, BNZ tissue biodistribution in a murine model and its pharmacokinetic profile in plasma were monitored. A bioanalytical high-performance liquid chromatography method with a UV detector (HPLC-UV) was developed and validated according to the European Medicines Agency for quantification of BNZ in organs and plasma samples prepared by liquidliquid extraction using ethyl acetate. The developed method was linear in the BNZ concentration, which ranged from 0.1 to 100.0 g/ml for plasma, spleen, brain, colon, heart, lung, and kidney and from 0.2 to 100.0 g/ml for liver. Validation assays demonstrated good stability for BNZ under all conditions evaluated. Pharmacokinetic parameters confirmed rapid, but low, absorption of BNZ after oral administration. Biodistribution assays demonstrated different maximum concentrations in organs and similar times to maximum concentration and mean residence times, with means of 40 min and 2.5 h, respectively. Therefore, the biodistribution of BNZ is extensive, reaching organs such as the heart and colon, which are the most relevant organs affected by Trypanosoma cruzi infection, and also the spleen, brain, liver, lungs, and kidneys. Simultaneous analyses of tissues and plasma indicated high BNZ metabolism in the liver. Our results suggest that low bioavailability, instead of inadequate biodistribution, could be responsible for therapeutic failure during the chronic phase of Chagas disease.

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A Simple and Efficient HPLC Method for Benznidazole Dosage in Human Breast Milk

Abstract: The method described is fast, specific, accurate, precise, and sufficiently sensitive in the clinical context for the quantification of BNZ in human milk. For all these reasons, it is suitable for clinical risk evaluation studies.

Cited by 10 publications

References 34 publications

Development of an ionic‐liquid‐based dispersive liquid–liquid microextraction method for the determination of antichagasic drugs in human breast milk: Optimization by central composite design

Development of an ionic‐liquid‐based dispersive liquid–liquid microextraction method for the determination of antichagasic drugs in human breast milk: Optimization by central composite design

Limited infant exposure to benznidazole through breast milk during maternal treatment for Chagas disease

Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice

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