Development and Validation of a Bioanalytical LC-MS/MS Method for Simultaneous Determination of Sirolimus in Porcine Whole Blood and Lung Tissue and Pharmacokinetic Application with Coronary Stents

Nguyen, Thi-Thao-Linh; Duong, Van-An; Vo, Dang-Khoa; Jo, Jeongae; Maeng, Han‐Joo

doi:10.3390/molecules26020425

Cited by 15 publications

(9 citation statements)

References 39 publications

(43 reference statements)

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“…The traditional approaches such as bronchoalveolar lavage (BAL) and whole lung tissue homogenates, employed to study lung tissue antimicrobial levels and have inherent limitations. Whole lung tissue homogenates require the consumption of a large number of experimental animals for PK studies ( 19 ). BAL alters the composition of the epithelial lining fluid and cannot provide sampling at all necessary time points from single animals ( 20 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

Lung microdialysis and in vivo PK/PD integration of cefquinome against Actinobacillus pleuropneumoniae in a porcine experimental lung infection model

Chen,

Li,

et al. 2024

Front. Vet. Sci.

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This study aim to explore the application of microdialysis in pharmacokinetic (PK) and pharmacodynamic (PD) integration of cefquinome against Actinobacillus pleuropneumoniae in a porcine experimental lung infection model. The model was established via intratracheal inoculation where average bacterial counts (CFU) in the lungs of infected pigs reached 6.57 log10 CFU/g after 3 h. The PK profiles of unbound cefquinome in lung dialysates were determined following intramuscular injection of single doses of 0.125, 0.25, 0.5, 1, 2, and 4 mg/kg. Lung dialysate samples were collected using microdialysis at a flow rate of 1.5 μL/min until 24 h. The PD studies were conducted over 24 h based on 10 intermittent dosing regimens and total daily doses ranged from 0.25 to 4 mg/kg and dosage intervals included 12 and 24 h. The lung tissue was collected after 24 h of treatment and homogenized for bacterial counts. The relationships between PK/PD parameters derived from lung dialysates and drug efficacy were analyzed using an inhibitory sigmoid Emax model. The percentage of time the free drug concentration exceeded the minimum inhibitory concentration (%fT > MIC) was the PK/PD index best describing the antimicrobial activity (R2 = 0.96) in the porcine experimental infection model. The %fT > MIC values required to achieve net bacterial stasis, 1, 2 and 3 log10 CFU/g reductions in the lung were 22.45, 28.86, 37.62, and 56.46%, respectively. Cefquinome exhibited time-dependent characteristics against A. pleuropneumoniae in vivo. These results provide valuable insights into the application of microdialysis in PK/PD integration model studies and optima regimen of cefquinome for the treatment of porcine respiratory diseases caused by A. pleuropneumoniae.

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Section: Discussionmentioning

confidence: 99%

Lung microdialysis and in vivo PK/PD integration of cefquinome against Actinobacillus pleuropneumoniae in a porcine experimental lung infection model

Chen,

Li,

et al. 2024

Front. Vet. Sci.

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“…The recovery was evaluated by comparing the mean peak areas of ARV-110 in the sample extracts (set 3) with those of the set 2 samples. The process efficiency was calculated by comparing the data in sets 3 and 1 [ 23 , 24 ].…”

Section: Methodsmentioning

confidence: 99%

Development of an LC-MS/MS Method for ARV-110, a PROTAC Molecule, and Applications to Pharmacokinetic Studies

et al. 2022

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ARV-110, a novel proteolysis-targeting chimera (PROTAC), has been reported to show satisfactory safety and tolerability for prostate cancer therapy in phase I clinical trials. However, there is a lack of bioanalytical assays for ARV-110 determination in biological samples. In this study, we developed and validated an LC-MS/MS method for the quantitation of ARV-110 in rat and mouse plasma and applied it to pharmacokinetic studies. ARV-110 and pomalidomide (internal standard) were extracted from the plasma samples using the protein precipitation method. Sample separation was performed using a C18 column and a mobile phase of 0.1% formic acid in distilled water–0.1% formic acid in acetonitrile (30:70, v/v). Multiple reaction monitoring was used to quantify ARV-110 and pomalidomide with ion transitions at m/z 813.4 → 452.2 and 273.8 → 201.0, respectively. The developed method showed good linearity in the concentration range of 2–3000 ng/mL with acceptable accuracy, precision, matrix effect, process efficiency, and recovery. ARV-110 was stable in rat and mouse plasma under long-term storage, three freeze-thaw cycles, and in an autosampler, but unstable at room temperature and 37 °C. Furthermore, the elimination of ARV-110 via phase 1 metabolism in rat, mouse, and human hepatic microsomes was shown to be unlikely. Application of the developed method to pharmacokinetic studies revealed that the oral bioavailability of ARV-110 in rats and mice was moderate (23.83% and 37.89%, respectively). These pharmacokinetic findings are beneficial for future preclinical and clinical studies of ARV-110 and/or other PROTACs.

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“…Sample separation was conducted using a flow rate of 0.2 mL/min and an 18-min gradient condition (0 min: 5% B, 5-9 min: 35% To quantify ergothioneine levels in pharmacokinetic samples, calibration curves were established by plotting the peak area ratios of ergothioneine to IS versus ergothioneine concentration using weighted (1/x) least-squares linear regression analysis. The method was validated for selectivity and linearity as previously described (Yoon et al 2020;Nguyen et al 2021). The results shown in Supplemental Figs.…”

Section: Quantitative Analysis Of Ergothioneinementioning

confidence: 99%

Effects of 1α,25-dihydroxyvitamin D3 on the pharmacokinetics and biodistribution of ergothioneine, an endogenous organic cation/carnitine transporter 1 substrate, in rats

Nguyen

Maeng

2022

J. Pharm. Investig.

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Purpose This study aimed to investigate the effects of 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) on the expression levels of organic cation/carnitine transporter 1 (OCTN1) as well as the pharmacokinetics and biodistribution of ergothioneine, an OCTN1 substrate, in rats. Methods Rats pretreated with 1,25(OH) 2 D 3 (2.56 nmol/kg/day) for four days were administered ergothioneine (2 mg/kg) intravenously. The expression levels of rat OCTN1 (rOCTN1) in organs were determined using real-time quantitative polymerase chain reaction. Ergothioneine levels in plasma, urine, and organs (with and without intravenous injection of exogenous ergothioneine) were determined using liquid chromatography-tandem mass spectrometry. Results 1,25(OH) 2 D 3 pretreatment resulted in a significant decrease in rOCTN1 mRNA expression levels in the kidney and brain, a significant increase in basal plasma levels of ergothioneine (from 48 h), and a significant decrease in the tissueplasma partition coefficient (K p ) in all tissues (except the heart and lungs) and the basal urine levels of ergothioneine. After intravenous administration, the pharmacokinetic profiles of ergothioneine were consistent with the basal levels of endogenous ergothioneine, with an increase in AUC ∞ by 85%, a significant decrease in total clearance by 49%, and a decrease in V ss by 32% in 1,25(OH) 2 D 3 -treated rats. The K p value and urinary recovery of ergothioneine also decreased in the 1,25(OH) 2 D 3treated group. Conclusion This study showed the effects of 1,25(OH) 2 D 3 on the expression and function of rOCTN1 by investigating the interaction between 1,25(OH) 2 D 3 and ergothioneine. Dose adjustment and possible changes in bioavailability should be considered before the co-administration of vitamin D or its active forms and OCTN1 substrates.

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Development and Validation of a Bioanalytical LC-MS/MS Method for Simultaneous Determination of Sirolimus in Porcine Whole Blood and Lung Tissue and Pharmacokinetic Application with Coronary Stents

Cited by 15 publications

References 39 publications

Lung microdialysis and in vivo PK/PD integration of cefquinome against Actinobacillus pleuropneumoniae in a porcine experimental lung infection model

Lung microdialysis and in vivo PK/PD integration of cefquinome against Actinobacillus pleuropneumoniae in a porcine experimental lung infection model

Development of an LC-MS/MS Method for ARV-110, a PROTAC Molecule, and Applications to Pharmacokinetic Studies

Effects of 1α,25-dihydroxyvitamin D3 on the pharmacokinetics and biodistribution of ergothioneine, an endogenous organic cation/carnitine transporter 1 substrate, in rats

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