A Sensitive and Selective LC–MS/MS Method for Quantitation of Ivermectin in Human, Mouse and Monkey Plasma: Clinical Validation

Chhonker, Yashpal S.; Ma, Ligeng; Edi, Constant; Murry, Daryl J.

doi:10.4155/bio-2018-0110

Cited by 12 publications

(7 citation statements)

References 38 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The plasma samples were collected before dosing and at 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours. Plasma samples were analyzed using the previously described validated liquid chromatography-mass spectrometric (LC-MS/MS) methods [ 19 – 21 ]. A visual predictive check with 1,000 replicates was performed after fixing structural and error parameters estimated by the final model.…”

Section: Methodsmentioning

confidence: 99%

Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis

et al. 2023

Self Cite

View full text Add to dashboard Cite

Background Ivermectin (IVM) is a broad–spectrum anthelmintic drug used to treat diseases caused by filarial worms, such as onchocerciasis and lymphatic filariasis (LF). IVM is part of a triple–drug therapy used by the Mass Drug Administration (MDA) as a preventive strategy to eradicate LF in sub–Saharan Africa. The drug shows high variability in drug exposure in previous pharmacokinetic studies. This study aims to build a population pharmacokinetic (PopPK) model to identify and quantify the possible sources of the variability of IVM exposure after a single–oral dose in LF–infected subjects and healthy individuals. Methodology / Principal findings In this analysis, 724 samples were collected from treatment–naïve Wuchereria bancrofti–infected (n = 32) and uninfected (n = 24) adults living in Côte d’Ivoire who had received one dose of IVM as a part of triple–drug therapy. PopPK analysis was conducted using Phoenix NLME 8.3 software. The Monte Carlo simulation based on the final model was performed to simulate drug exposure among different dosing groups (200 μg/kg, 18 mg, and 36 mg). A two–compartment model with zero–order dose input into the absorption compartment with a lag time function followed by first–order absorption and linear elimination best described the IVM’s pharmacokinetic (PK) parameters. The final model identifies that the PK parameters of IVM are not affected by LF infection. Sex was a significant covariate on the peripheral volume of distribution (Vp/F, 53% lower in men than in women). IVM drug exposure shows linear pharmacokinetic behavior among the simulated dosing groups with similar drug exposure based on sex. Conclusion/Significance We have developed a PopPk model to describe and identify possible sources of the variability of IVM exposure. To our knowledge, this is the first PopPK study of IVM in patients with LF. Trial registration NCT02845713; NCT03664063

show abstract

Section: Methodsmentioning

confidence: 99%

Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…The addition of 0.1% AA to both the aqueous and organic phase (acetonitrile) resulted in a better signal for DORA, compared to water and 0.1% FA, whereas for IVER the best results were obtained by using no organic modifier (see Figure S1A). MOXI was not tested during the initial experiment, but Chhonker et al 2018 [24] also previously reported 0.1%AA as an organic modifier for MOXI. By reducing the AA concentration from 0.1% to 0.01%, the signal intensity for IVER and MOXI increased, whereas a decreased signal intensity for DORA was observed (see Figure S1B).…”

Section: Internal Standardizationmentioning

confidence: 99%

“…LC-MS/MS also allows accurate simultaneous analysis of mixtures in biological matrices, such as plasma. A few studies have been reported for quantification of MLs using LC-MS/MS methods in biological matrices, such as in milk [20], lamb tissues [21,22], and lamb serum [23], human [24], dog [25], and calf [26] plasma.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Reliable UHPLC-MS/MS Method for Simultaneous Quantification of Macrocyclic Lactones in Bovine Plasma

et al. 2022

View full text Add to dashboard Cite

A fast, accurate and reliable ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method was developed for simultaneous quantification of ivermectin (IVER), doramectin (DORA), and moxidectin (MOXI) in bovine plasma. A priority for sample preparation was the eradication of possible infectious diseases to avoid travel restrictions. The sample preparation was based on protein precipitation using 1% formic acid in acetonitrile, followed by Ostro® 96-well plate pass-through sample clean-up. The simple and straightforward procedure, along with the short analysis time, makes the current method unique and suitable for a large set of sample analyses per day for PK studies. Chromatographic separation was performed using an Acquity UPLC HSS-T3 column, with 0.01% acetic acid in water and methanol, on an Acquity H-Class ultra-high performance liquid chromatograph (UHPLC) system. The MS/MS instrument was a Xevo TQ-S® mass spectrometer, operating in the positive electrospray ionization mode and two multiple reaction monitoring (MRM) transitions were monitored per component. The MRM transitions of m/z 897.50 > 753.4 for IVER, m/z 921.70 > 777.40 for DORA and m/z 640.40 > 123.10 for MOXI were used for quantification. The method validation was performed using matrix-matched calibration curves in a concentration range of 1 to 500 ng/mL. Calibration curves fitted a quadratic regression model with 1/x2 weighting (r ≥ 0.998 and GoF ≤ 4.85%). Limits of quantification (LOQ) values of 1 ng/mL were obtained for all the analytes, while the limits of detection (LOD) were 0.02 ng/mL for IVER, 0.03 ng/mL for DORA, and 0.58 ng/mL for MOXI. The results of within-day (RSD < 6.50%) and between-day (RSD < 8.10%) precision and accuracies fell within acceptance ranges. No carry-over and no peak were detected in the UHPLC-MS/MS chromatogram of blank samples showing good specificity of the method. The applicability of the developed method was proved by an analysis of the field PK samples.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

A Sensitive and Selective LC–MS/MS Method for Quantitation of Ivermectin in Human, Mouse and Monkey Plasma: Clinical Validation

Cited by 12 publications

References 38 publications

Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis

Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis

Development and Validation of a Reliable UHPLC-MS/MS Method for Simultaneous Quantification of Macrocyclic Lactones in Bovine Plasma

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

Contact Info

Product

Resources

About