Novel LC-MS/MS analysis of the GLP-1 analog semaglutide with its application to pharmacokinetics and brain distribution studies in rats

Lee, Tae Suk; Park, Eun Ji; Choi, Minkyu; Oh, Hyun Seok; An, Yejin; Kim, Tae-Hyung; Kim, So Yeon; Shin, Beom Soo; Shin, Soyoung

doi:10.1016/j.jchromb.2023.123688

Cited by 16 publications

(7 citation statements)

References 27 publications

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“…Because there were no articles about the analytical method of plinabulin or similar compounds, we have not compared the LLOQ of our study with others. In general, LLOQ of 0.5 ng/mL is sensitive for bioanalytical methods [ 16 , 17 , 18 , 19 , 20 ]. In our study, the LLOQ was 0.5 ng/mL, and the value of the signal-to-noise ratio of LLOQ was greater than 10.…”

Section: Resultsmentioning

confidence: 99%

Development and Validation of a Novel UHPLC-MS/MS Method for the Quantification of Plinabulin in Plasma and Its Application in a Pharmacokinetic Study with Leukopenic Rats

Niu

Chen

et al. 2023

Pharmaceuticals

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Plinabulin, a new antitumor drug developed from marine natural products that targets microtubules in cancer cells, is currently being tested in a phase III clinical study. Plinabulin has been clinically proven to be effective on leukopenia. However, to our knowledge, there are no reports investigating the pharmacokinetics of plinabulin in individuals with leukopenia and healthy individuals. In this study, we developed a rapid and sensitive UHPLC-MS/MS method for the detection of plinabulin for the first time. Using a novel cyclophosphamide-induced leukopenia model, we investigated the differences in the pharmacokinetic characteristics of plinabulin between rats with leukopenia and normal rats. Plinabulin and propranolol (IS) peaks were separated by gradient elution for a total run time of 5 min. The methodological validation showed a good accuracy (101.96–109.42%) and precision (RSD ≤ 5.37%) with the lower limit of quantification at 0.5 ng/mL. The recovery of plinabulin was between 91.99% and 109.75% (RSD ≤ 7.92%). The values of the area under the plasma concentration-time curve (AUC0-t) for leukopenia groups and control groups at doses of 0.5 mg/kg, 1 mg/kg, and 3 mg/kg were 148.89 ± 78.74 h·μg/L and 121.75 ± 31.56 h·μg/L; 318.15 ± 40.00 h·μg/L and 272.06 ± 42.85 h·μg/L; and 1432.43 ± 197.47 h·μg/L and 1337.12 ± 193.56 h·μg/L; respectively. The half-lives (t1/2s) of plinabulin were 0.49–0.72 h for leukopenia groups and 0.39–0.70 h for control groups at three doses, and the clearance rates (CLs) of plinabulin were 2.13–3.87 L/h/kg for leukopenia groups and 2.29–4.23 L/h/kg for control groups. Pharmacokinetic results showed that there was no significant pharmacokinetic difference between the normal group and the leukopenia group. Based on the power model, plinabulin exhibits a lack of dose proportionality over the dose range of 0.5–3 mg/kg after intravenous administration. This study provides guidance for the development of plinabulin as a potential candidate for the treatment of chemotherapy-induced leukopenia.

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Section: Resultsmentioning

confidence: 99%

Development and Validation of a Novel UHPLC-MS/MS Method for the Quantification of Plinabulin in Plasma and Its Application in a Pharmacokinetic Study with Leukopenic Rats

Niu

Chen

et al. 2023

Pharmaceuticals

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“…Moreover, SEM demonstrates remarkable stability, with less than 2% degradation in serum and less than 12% in the whole brain over the specified time frame of 60 min [ 18 , 54 , 55 , 56 , 57 ]. In another study [ 58 ], the stability of SEM was evaluated under four different storage conditions (i.e., 4 h at room temperature, 7 days at −70 °C, 24 h in the autosampler, and freeze/thaw cycles). It was found that SEM exhibited average stability ranging from 93.94% to 106.13% in plasma and 91.64% to 107.31% in brain tissue, with no significant deviations observed under all tested conditions [ 58 ].…”

Section: Sem Pharmacokinetics In Animal Modelsmentioning

confidence: 99%

“…In another study [ 58 ], the stability of SEM was evaluated under four different storage conditions (i.e., 4 h at room temperature, 7 days at −70 °C, 24 h in the autosampler, and freeze/thaw cycles). It was found that SEM exhibited average stability ranging from 93.94% to 106.13% in plasma and 91.64% to 107.31% in brain tissue, with no significant deviations observed under all tested conditions [ 58 ]. Such robust stability positions SEM favorably when compared to other IRAs like DA3-CH, which experiences higher degradation rates, indicating that SEM remains stable for routine analysis.…”

Section: Sem Pharmacokinetics In Animal Modelsmentioning

confidence: 99%

“…Such robust stability positions SEM favorably when compared to other IRAs like DA3-CH, which experiences higher degradation rates, indicating that SEM remains stable for routine analysis. These structural and stability distinctions underscore SEM’s potential advantages in bioavailability and durability, contributing to its unique profile within the landscape of insulin receptor agonists [ 18 , 58 , 59 , 60 ].…”

Section: Sem Pharmacokinetics In Animal Modelsmentioning

confidence: 99%

“…Following intravenous administration, SEM plasma concentrations exhibited a multi-exponential decline, with an average half-life (T1/2) of 9.26 ± 1.06 h and an average clearance and distribution volume estimated at 0.21 mL/min/kg (0.10 L/kg) [ 58 ]. In a study on CD-1 mice conducted by Salameh’s team, the serum clearance of SEM labeled with mCi Na 125I was 2.5 h. Concerning subcutaneous administration, SEM plasma concentration increased gradually, reaching peak concentration between 3 and 12 h, and decreased with an average half-life of 7.22–8.99 h [ 18 ].…”

Section: Sem Pharmacokinetics In Animal Modelsmentioning

confidence: 99%

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Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models

Meca,

Boboc,

Mititelu-Tartau

et al. 2024

CIMB

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Semaglutide (SEM), a glucagon-like peptide-1 receptor agonist, has garnered increasing interest for its potential therapeutic effects in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This review provides a comprehensive description of SEM’s mechanism of action and its effects in preclinical studies of these debilitating conditions. In animal models of AD, SEM has proved beneficial effects on multiple pathological hallmarks of the disease. SEM administration has been associated with reductions in amyloid-beta plaque deposition and mitigation of neuroinflammation. Moreover, SEM treatment has been shown to ameliorate behavioral deficits related to anxiety and social interaction. SEM-treated animals exhibit improvements in spatial learning and memory retention tasks, as evidenced by enhanced performance in maze navigation tests and novel object recognition assays. Similarly, in animal models of PD, SEM has demonstrated promising neuroprotective effects through various mechanisms. These include modulation of neuroinflammation, enhancement of mitochondrial function, and promotion of neurogenesis. Additionally, SEM has been shown to improve motor function and ameliorate dopaminergic neuronal loss, offering the potential for disease-modifying treatment strategies. Overall, the accumulating evidence from preclinical studies suggests that SEM holds promise as a novel therapeutic approach for AD and PD. Further research is warranted to elucidate the underlying mechanisms of SEM’s neuroprotective effects and to translate these findings into clinical applications for the treatment of these devastating neurodegenerative disorders.

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Single‐Administration Self‐Boosting Microneedle Patch for the Treatment of Obesity

Singh,

Vinikoor,

Sharma

et al. 2024

Advanced Therapeutics

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Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are one of the most effective treatments for obesity. The current therapy associated with repeated subcutaneous injections to maintain the drug therapeutic effect causes patient compliance issues and raises environmental concerns (due to sharp biohazard waste from disposed syringes/needles). Herein, a programmable scheduled release microneedles (PSR‐MNs) system is reported for delivering Semaglutide (a GLP‐1 RA agent with a half‐life of ≈7 days) to manage and treat obesity. A single skin administration of a PSR‐MNs patch (2 cm × 2 cm) that contains 4 programmable core‐shell microneedle (MNs) patches (1 cm2 each, so‐called pixels) enables the repeated release of Semaglutide every 7 days and sustains the drug efficacy for an unprecedented one‐month period, simulating the effect of using four bolus injections spaced 7 days apart. This PSR‐MNs system provides an advanced injection‐free platform to significantly enhance the current treatment of obesity with GLP‐1RAs, addressing concerns related to pain, needle phobia, high cost, and the need of medical facilities/personnel in traditional injections to administer the drug.

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Novel LC-MS/MS analysis of the GLP-1 analog semaglutide with its application to pharmacokinetics and brain distribution studies in rats

Cited by 16 publications

References 27 publications

Development and Validation of a Novel UHPLC-MS/MS Method for the Quantification of Plinabulin in Plasma and Its Application in a Pharmacokinetic Study with Leukopenic Rats

Development and Validation of a Novel UHPLC-MS/MS Method for the Quantification of Plinabulin in Plasma and Its Application in a Pharmacokinetic Study with Leukopenic Rats

Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models

Single‐Administration Self‐Boosting Microneedle Patch for the Treatment of Obesity

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