Development and validation of an LC-MS/MS method for the analysis of ivermectin in plasma, whole blood, and dried blood spots using a fully automatic extraction system

Duthaler, Urs; Suenderhauf, Claudia; Gaugler, Stefan; Vetter, Beatrice; Krähenbühl, Stephan; Hammann, Felix

doi:10.1016/j.jpba.2019.04.007

Cited by 26 publications

(17 citation statements)

References 18 publications

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“…We first examined the pharmacokinetics and bio-distribution of TMP269, the class IIa-HDAC inhibitor we selected for this study. After intraperitoneal injection of 25 mg/kg body weight of TMP269 dissolved in Polyethylenglycol 300 (PEG300) (500 µl/Kg) and N-Methyl-2-pyrrolidone (NMP) (250 µL/Kg), blood and/or skeletal muscles were collected at different time points and the content of TMP269 was quantified by liquid chromatography tandem mass spectrometry (21). The peak blood concentration of TMP269 was achieved approximately 1 hour after injection.…”

Section: Effect Of Tmp269 and 5-aza-2-deoxycytidine On The In Vivo Mu...mentioning

confidence: 99%

“…The levels of TMP269 in blood and in skeletal muscle were quantified by high pressure liquid chromatography tandem mass spectrometry (LC-MS/MS) as described (21). Briefly, A Shimadzu LC system (Kyoto, Japan) was used, TMP269 and TMP195 (internal standard, IS) were analyzed by positive electrospray ionization and multiple reaction monitoring (MRM).…”

Section: Compliance Withmentioning

confidence: 99%

“…injection of 25 mg/kg body weight of TMP269 dissolved in PEG300 (500 µl/kg) and NMP (250 µl/kg) results in accumulation of the drug in blood and skeletal muscles. Samples were collected at different time points and the content of TMP269 was quantified by LC-MS/MS ( Duthaler et al, 2019 ). The peak blood concentration of TMP269 was achieved approximately 1 hr after injection.…”

Section: Appendix 1—figurementioning

confidence: 99%

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Improvement of muscle strength in a mouse model for congenital myopathy treated with HDAC and DNA methyltransferase inhibitors

Ruiz¹,

Benucci²,

Duthaler

et al. 2022

eLife

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To date there are no therapies for patients with congenital myopathies, muscle disorders causing poor quality of life of affected individuals. In approximately 30% of the cases, patients with congenital myopathies carry either dominant or recessive mutations in the RYR1 gene; recessive RYR1 mutations are accompanied by reduction of RyR1 expression and content in skeletal muscles and are associated with fiber hypotrophy and muscle weakness. Importantly, muscles of patients with recessive RYR1 mutations exhibit increased content of class II histone de-acetylases and of DNA genomic methylation. We recently created a mouse model knocked-in for the p.Q1970fsX16+p.A4329D RyR1 mutations, which are isogenic to those carried by a severely affected child suffering from a recessive form of RyR1-related multi-mini core disease. The phenotype of the RyR1 mutant mice recapitulates many aspects of the clinical picture of patients carrying recessive RYR1 mutations. We treated the compound heterozygous mice with a combination of two drugs targeting DNA methylases and class II histone de-acetylases. Here we show that treatment of the mutant mice with drugs targeting epigenetic enzymes improves muscle strength, RyR1 protein content and muscle ultrastructure. This study provides proof of concept for the pharmacological treatment of patients with congenital myopathies linked to recessive RYR1 mutations.

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Section: Effect Of Tmp269 and 5-aza-2-deoxycytidine On The In Vivo Mu...mentioning

confidence: 99%

Section: Compliance Withmentioning

confidence: 99%

Section: Appendix 1—figurementioning

confidence: 99%

See 1 more Smart Citation

Improvement of muscle strength in a mouse model for congenital myopathy treated with HDAC and DNA methyltransferase inhibitors

Ruiz¹,

Benucci²,

Duthaler

et al. 2022

eLife

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“…Usually, raw analytical data from plasma-based matrices can be used as such for quantitation and chemical-clinical correlations [41][42][43][44], while those obtained from blood-based matrices have to be elaborated to account for analyte dilution (correlated to hematocrit), and for red blood cell/plasma partitioning [45][46][47][48][49]. For the samples presented here, no direct hematocrit measurement was carried out: fixed hematocrit values were used, equal to 38% for females and 48% for males.…”

Section: Analysis Of Real Samples and Accuracymentioning

confidence: 99%

Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption

2020

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Reliable, feasible analytical methods are needed for forensic and anti-doping testing of cocaine and its most important metabolites, benzoylecgonine, ecgonine methyl ester, and cocaethylene (the active metabolite formed in the presence of ethanol). An innovative workflow is presented here, using minute amounts of dried blood or plasma obtained by volumetric absorptive microsampling (VAMS), followed by miniaturized pretreatment by dispersive pipette extraction (DPX) and LC-MS/MS analysis. After sampling 20 µL of blood or plasma with a VAMS device, the sample was dried, extracted, and loaded onto a DPX tip. The DPX pretreatment lasted less than one minute and after elution with methanol the sample was directly injected into the LC-MS/MS system. The chromatographic analysis was carried out on a C8 column, using a mobile phase containing aqueous formic acid and acetonitrile. Good extraction yield (> 85%), precision (relative standard deviation, RSD < 6.0%) and matrix effect (< 12%) values were obtained. Analyte stability was outstanding (recovery > 85% after 2 months at room temperature). The method was successfully applied to real blood and plasma VAMS, with results in very good agreement with those of fluid samples. The method seems suitable for the monitoring of concomitant cocaine and ethanol use by means of plasma or blood VAMS testing.

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“…Iglesias et al used the same method for soil and cattle feces [13]. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) has also been shown in several studies to be useful for multiple matrixes such as plasma, milk, liver, and whole blood [14][15][16][17][18][19][20]. Liquid chromatography-electrospray ionization-mass spectrometry/mass spectrometry (LC-ESI-MS/MS) has also been used to detect macrocyclic lactones in fsh muscle [14].…”

Section: Introductionmentioning

confidence: 99%

A New Method for Ivermectin Detection and Quantification through HPLC in Organic Matter (Feed, Soil, and Water)

Heredero

Segato

Menotta

et al. 2023

Journal of Analytical Methods in Chemistry

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Ivermectin is a macrocyclic lactone widely used in veterinary medicine for its broad-spectrum antiparasitic properties. It has been proven to be effective and safe. The purpose of this study was to develop a high-performance liquid chromatography method with a diode array detector for ivermectin screening in feed and water for animal consumption. Furthermore, the objective was to quantify ivermectin levels that were higher than 0.5 mg/kg in solid matrixes and 0.1 mg/kg in water. Doramectin was used as process standard. Samples were extracted using solid phase extraction with silica and C-18 columns. The method involved the use of high-performance liquid chromatography (HPLC) with a diode array detector (DAD). The results were interpreted using a calibration curve built with ivermectin standards at multiple concentrations (0.5, 1, 2, 5, and 12.5 mg/kg). Statistical evaluation of data was done using ANOVA. The data analysis showed that the linear regression was highly significant ( P < 0.001 ), the intercept values were not significantly different from zero, and the correlation coefficient values (>0.999) indicated excellent linearity. Further tests demonstrated that this method is also useful when studying soil matrixes. The soil was dried and analyzed in the same way as feed; the same recoveries were realized on the spiked samples. The method is easy, inexpensive, precise, and repeatable; it requires very small amounts of sample.

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Development and validation of an LC-MS/MS method for the analysis of ivermectin in plasma, whole blood, and dried blood spots using a fully automatic extraction system

Cited by 26 publications

References 18 publications

Improvement of muscle strength in a mouse model for congenital myopathy treated with HDAC and DNA methyltransferase inhibitors

Improvement of muscle strength in a mouse model for congenital myopathy treated with HDAC and DNA methyltransferase inhibitors

Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption

A New Method for Ivermectin Detection and Quantification through HPLC in Organic Matter (Feed, Soil, and Water)

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