Simultaneous Determination of Celecoxib, Dezocine and Dexmedetomidine in Beagle Plasma Using UPLC-MS/MS Method and the Application in Pharmacokinetics

Hu, Jie; Su, Xin-juan; Si, Hui-Ling; Song, Ruixiang; Zhang, Fang; Qiu, Xiangjun; Chen, Xingpeng

doi:10.2147/dddt.s314562

Cited by 8 publications

(4 citation statements)

References 21 publications

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“…Therefore, it is often used in the detection of biological samples, the study of pharmacokinetics and DDI. 15 , 20 , 21 …”

Section: Resultsmentioning

confidence: 99%

The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique

Wang¹,

Zhou²,

Su³

et al. 2021

DDDT

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Background A new UPLC-MS/MS technique for the determination of ripretinib in beagle dog plasma was developed, and the pharmacokinetic effects of voriconazole and itraconazole on ripretinib in beagle dogs were studied. Methods After extraction with ethyl acetate under alkaline conditions, ripretinib was detected using avapritinib as the internal standard (IS). The mobile phases were 0.1% formic acid-acetonitrile. The scanning method was multi-reaction monitoring using ESI+ source, and the ion pairs for ripretinib and IS were m/z 509.93→416.85 and 499.1→482.09, respectively. This animal experiment adopted a three period self-control experimental design. In the first period, ripretinib was orally administered to six beagle dogs at a dose of 5 mg/kg. In the second period, the same six beagle dogs were orally given itraconazole at a dose of 7 mg/kg, after 30 min, ripretinib was orally given. In the third period, voriconazole at a dose of 7 mg/kg was given orally, and then ripretinib was orally given. At different time points, the blood samples were collected. The concentration of ripretinib was detected, and the pharmacokinetic parameters of ripretinib were calculated. Results Ripretinib had a good linear relationship in the range of 1–1000 ng/mL. The precision, accuracy, recovery, matrix effect and stability met the requirements of the guiding principles. After erdafitinib combined with itraconazole, the C max and AUC 0→t of ripretinib increased by 38.35% and 36.36%, respectively, and the t 1/2 was prolonged to 7.53 h. After ripretinib combined with voriconazole, the C max and AUC 0→t of ripretinib increased by 37.44% and 25.52%, respectively, and the t 1/2 was prolonged to 7.33 h. Conclusion A new and reliable UPLC-MS/MS technique was fully optimized and developed to detect the concentration of ripretinib in beagle dog plasma. Itraconazole and voriconazole could inhibit the metabolism of ripretinib in beagle dogs and increase the plasma exposure of ripretinib.

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“…Therefore, it is often used in the detection of biological samples, the study of pharmacokinetics and DDI. 15 , 20 , 21 …”

Section: Resultsmentioning

confidence: 99%

The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique

Wang¹,

Zhou²,

Su³

et al. 2021

DDDT

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“…Dex has a significant analgesic effect, which can reduce the use of morphine on the first day after surgery, relieve the pain of patients, and reduce the occurrence of postoperative nausea, vomiting, dizziness, and other adverse reactions. Dex combined with dezocine is very safe in monitoring anesthesia, and the analgesic effect is significantly increased when the two drugs are used in combination, but the sedative effect does not superimpose [24,25]. This study found that the onset time of sensory block, recovery time, and time spent in PACU in the experimental group were significantly shorter than those in the control group, the time of anesthesia maintenance was significantly greater than that in the control group, the use of intravenous analgesics was also significantly lower than that in the control group, and the incidence of adverse reactions (nausea, vomiting, dizziness) was also significantly smaller than that in the control group.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Postoperative Analgesia in Patients with Thoracolumbar Compression Fracture without Nerve Injury by CT using Filtered Back Projection Reconstruction Algorithm

Fan¹,

Ji²,

Qian³

et al. 2022

jist

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To study computed tomography (CT) images based on filtered back projection (FBP) reconstruction algorithm, and analyze the clinical efficacy of dexmedetomidine (Dex) combined with dezocine in thoracolumbar vertebral compression fractures patients without nerve injury during surgery, 75 patients with thoracolumbar vertebral compression fractures were divided into the experimental group (dexmedetomidine combined with dezocine intravenous injection) and the control group (dezocine intravenous injection). The anterior/middle vertebral height and kyphotic angle, assessment of thoracolumbar function (Japanese Orthopaedic Association Score) (JOA)/pain level (visual analogue scale) (VAS), onset of sensory block/palinesthesia/post-anesthesia care unit (PACU) stay/duration of anesthesia, dosage of intravenous analgesic drugs/rate of supplementary analgesics, adverse reactions, and other indicators were observed. It found that CT image was clearer and the resolution was higher after algorithm processing; after treatment, the height of anterior/middle vertebral height in the experimental group was greater than that in the control group, P < 0.05; JOA was greater than that in the control group, and VAS score was less than that in the control group, P < 0.05; the time of onset of sensory block/palinesthesia/PACU stay, the dosage of intravenous analgesic drugs/the rate of supplementary analgesic drugs, incidence of adverse reactions were less than those in the control group, and duration of anesthesia was greater than that in the control group, P < 0.05. Therefore, this drug has a significant analgesic effect on patients with thoracolumbar fracture after surgery.

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“…Therefore, it is often used in the detection of drug concentration in biological samples, the study of pharmacokinetics and DDI. 19,20 Fedratinib and upadacitinib were JAK inhibitors. Fedratinib was a selective JAK2 inhibitor for the treatment of adult patients with myelofibrosis (MF).…”

Section: Methods Validation and Improvementmentioning

confidence: 99%

Development of an UPLC-MS/MS Method for the Quantitative Analysis of Upadacitinib in Beagle Dog Plasma and Pharmacokinetics Study

Wang¹,

Zhao²,

Fan³

et al. 2021

DDDT

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Background Upadacitinib, a novel selective Janus kinase 1 (JAK1) inhibitor, has been recently approved by the US FDA for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the quantitative analysis of upadacitinib in beagle dog plasma was developed and validated. Methods Upadacitinib and fedratinib (internal standard, IS) were extracted with ethyl acetate under alkaline condition and then separated and detected. The chromatographic column was Waters Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm), the mobile phase was acetonitrile and 0.1% formic acid in water with gradient elution procedure, and the flow rate was 0.40 mL/min. Under the positive ion mode, upadacitinib and IS were monitored by multiple reaction monitoring (MRM) as the following mass transition pairs: m/z 447.00 → 361.94 for upadacitinib and m/z 529.82 → 141.01 for IS. Results In the concentration range of 1–500 ng/mL, upadacitinib had good linearity, and the lower limit of quantification (LLOQ) was 1 ng/mL. The RSD of the intra- and inter-day precision was less than 10.03%, and the RE of accuracy was −3.79% to 2.58%. The extraction recovery of upadacitinib was more than 80%, the matrix effect was around 100%, and upadacitinib was found to be stable. Conclusion The novel optimized UPLC-MS/MS assay was an effective tool for the determination of upadacitinib and had been successfully applied to the pharmacokinetic study of upadacitinib in beagle dogs, and this method would also be used to study DDIs.

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Simultaneous Determination of Celecoxib, Dezocine and Dexmedetomidine in Beagle Plasma Using UPLC-MS/MS Method and the Application in Pharmacokinetics

Cited by 8 publications

References 21 publications

The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique

The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique

Evaluation of Postoperative Analgesia in Patients with Thoracolumbar Compression Fracture without Nerve Injury by CT using Filtered Back Projection Reconstruction Algorithm

Development of an UPLC-MS/MS Method for the Quantitative Analysis of Upadacitinib in Beagle Dog Plasma and Pharmacokinetics Study

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