&lt;p&gt;Simultaneous Determination of Parecoxib and Its Metabolite Valdecoxib Concentrations in Beagle Plasma by UPLC-MS/MS and Application for Pharmacokinetics Study&lt;/p&gt;

Li, Shuang-long; Zhu, Yongliang; Zhu, Congmin; Li, Shaobin; Li, Zi-heng; Qiu, Xiangjun

doi:10.2147/dddt.s226349

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…UPLC-MS/MS is a common method for the detection of biological samples, which has the advantages of rapidity, sensitivity, and accurateness. The UPLC-MS/MS method has been reported for the simultaneous determination of parecoxib and its metabolite valdecoxib [ 22 , 23 ]. In this experiment, based on these methods, a rapid, sensitive, and accurate detection method was established and validated for specificity, linearity, precision, accuracy, recovery, and stability.…”

Section: Methodsmentioning

confidence: 99%

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

Guo

et al. 2020

BioMed Research International

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A sensitive and reliable ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of parecoxib and its metabolite valdecoxib in beagles. The effects of dexmedetomidine on the pharmacokinetics of parecoxib and valdecoxib in beagles were studied. The plasma was precipitated by acetonitrile, and the two analytes were separated on an Acquity UPLC BEH C18 column (2.1 mm×50 mm, 1.7 μm); the mobile phase was acetonitrile and 0.1% formic acid with gradient mode, and the flow rate was 0.4 mL/min. In the negative ion mode, the two analytes and internal standard (IS) were monitored by multiple reaction monitoring (MRM), and the mass transition pairs were as follows: m/z 369.1→119.1 for parecoxib, m/z 313.0→118.0 for valdecoxib, and m/z 380.0→316.0 for celecoxib (IS). Six beagles were designed as a double cycle self-control experiment. In the first cycle, after intramuscular injection of parecoxib 1.33 mg/kg, 1.0 mL blood samples were collected at different times (group A). In the second cycle, the same six beagles were intravenously injected with 2 μg/kg dexmedetomidine for 7 days after one week of washing period. On day 7, after intravenous injection of 2 μg/kg dexmedetomidine for 0.5 hours, 6 beagle dogs were intramuscularly injected with 1.33 mg/kg parecoxib, and blood samples were collected at different time points (group A). The concentration of parecoxib and valdecoxib was detected by UPLC-MS/MS, and the main pharmacokinetic parameters were calculated by DAS 2.0 software. Under the experimental conditions, the method has a good linear relationship for both analytes. The interday and intraday precision was less than 8.07%; the accuracy values were from -1.20% to 2.76%. Cmax of parecoxib in group A and group B was 2148.59±406.13 ng/mL and 2100.49±356.94 ng/mL, t1/2 was 0.85±0.36 h and 0.85±0.36 h, and AUC0‐t was 2429.96±323.22 ng·h/mL and 2506.38±544.83 ng·h/mL, respectively. Cmax of valdecoxib in group A and group B was 2059.15±281.86 ng/mL and 2837.39±276.78 ng/mL, t1/2 was 2.44±1.55 h and 2.91±1.27 h, and AUC0‐t was 4971.61±696.56 ng·h/mL and 6770.65±453.25 ng·h/mL, respectively. There was no significant change in the pharmacokinetics of parecoxib in groups A and B. Cmax and AUC0−∞ of valdecoxib in group A were 37.79% and 36.19% higher than those in group B, respectively, and t1/2 was increased from 2.44 h to 2.91 h. Vz/F and CLz/F were correspondingly reduced, respectively. The developed UPLC-MS/MS method for simultaneous determination of parecoxib and valdecoxib in beagle plasma was specific, accurate, rapid, and suitable for the pharmacokinetics and drug-drug interactions of parecoxib and valdecoxib. Dexmedetomidine can inhibit the metabolism of valdecoxib in beagles and increase the exposure of valdecoxib, but it does not affect the pharmacokinetics of parecoxib.

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Section: Methodsmentioning

confidence: 99%

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

Guo

et al. 2020

BioMed Research International

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“…[1,13] It can clarify the changing trend of drug concentration in the tissues with the time of administration, and then evaluate in vivo targeting and tissue accumulation of the drug, [14] and judge the safety and effectiveness of the drug. [14,15] This study mainly explored the plasma pharmacokinetics, absorption, distribution, metabolism, and excretion properties of CYP in preclinical animals by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The research contents included: (i) Plasma pharmacokinetic characteristics and F of intramuscular CYP in mice and beagles after single intravenous and intramuscular injection of different doses of CYP; (ii) The distribution of CYP in the main tissues and organs of mice after intramuscular injection; (iii) Excretion of prototype drug through urine and feces after intramuscular injection of CYP in mice.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of cyproheptadine hydrochloride in mice and beagle dogs, tissue distribution, and excretion properties of cyproheptadine hydrochloride in mice

Liu,

Cui,

Zhou

2024

Separation Science Plus

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Cyproheptadine hydrochloride (CYP) is a typical antihistamine with antiserotonergic, blocking H1 receptor, anticholine, anti‐inflammatory and anti‐allergic effects. To investigate the pharmacokinetics, biodistribution, and excretion, the liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method was established and validated the CYP concentrations in the plasma of beagle dogs and the biological matrix of mice. CYP was quickly absorbed into the bloodstream and widely distributed to various tissues. The area under the curve (AUC)0–t and peak concentration of CYP were increased with the dose after administration. At the equal dose, the bioavailability of intramuscular injection in mice and beagle dogs was 81.1% and 79.1%. The tissue distribution experiments suggested that CYP would not accumulate for a long time in vivo. CYP levels in tissues peaked after 15 min of injection, and the drug concentrations in the kidney and lung were higher than those in other tissues. For excretion, the cumulative urinary excretion of CYP within 156 h after intramuscular injection in mice accounted for (1.2 ± 0.1)% of the total administration dose. The feces excretion of the drug prototype was below the lower limit of quantitation. High sensitivity and strong specificity are observed based on the established method of LC‐MS/MS, which was successfully applied to the pharmacokinetics, tissue distribution, and excretion studies of CYP.

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“…UPLC-MS/MS had been widely used for the determination of drug concentrations in various biological matrices, which had many advantages such as short time, high sensitivity and strong specificity. 15,16 This paper presented a new, rapid and accurate UPLC-MS/MS method for determining the concentration of selinexor and investigated the effects of posaconazole on the pharmacokinetics of selinexor using fedratinib as the internal standard (IS, Figure 1B).…”

Section: Introductionmentioning

confidence: 99%

Establishment and Verification of UPLC-MS/MS Technique for Pharmacokinetic Drug–Drug Interactions of Selinexor with Posaconazole in Rats

Zhou¹,

Wang²,

Zhou³

et al. 2021

DDDT

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Background: A method for the determination of selinexor by UPLC-MS/MS was established to study the effect of posaconazole on the pharmacokinetics of selinexor in rats. Methods: The experiment rats were divided into group A (0.5% CMC-Na) and group B (posaconazole, 20 mg/kg), 6 rats in each group. 30 minutes after administration of 0.5% CMC-Na or posaconazole, all the rats were given selinexor (8 mg/kg), and plasma samples were collected. The plasma samples underwent acetonitrile protein precipitation, and were separated by UPLC on an Acquity UPLC BEH C18 column with gradient elution. Acetonitrile and 0.1% formic acid were used as the mobile phases. The analyte detection was used a Xevo TQ-S triple quadrupole tandem mass spectrometer and multiple reaction monitoring (MRM) for analyte monitoring. We use acetonitrile for protein precipitation. Results: Selinexor had good linearity (1.0-1000 ng/mL, r 2 = 0.996 2), and the accuracy and precision, recovery rate and matrix effects(ME) were also met the FDA approval guidelines. Compared with group A, the C max , AUC (0−t) and AUC (0−∞) of selinexor in group B increased by 60.33%, 48.28% and 48.27%, and T max increased by 53.92%, CLz/F reduced by 32.08%. Conclusion: This bioanalysis method had been applied to the study of drug interactions in rats. It was found that posaconazole significantly increased the concentration of selinexor in rats. Therefore, when selinexor and posaconazole are combined, we should pay attention to the possible drug-drug interactions to reduce adverse reactions.

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<p>Simultaneous Determination of Parecoxib and Its Metabolite Valdecoxib Concentrations in Beagle Plasma by UPLC-MS/MS and Application for Pharmacokinetics Study</p>

Cited by 7 publications

References 29 publications

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

Pharmacokinetics of cyproheptadine hydrochloride in mice and beagle dogs, tissue distribution, and excretion properties of cyproheptadine hydrochloride in mice

Establishment and Verification of UPLC-MS/MS Technique for Pharmacokinetic Drug–Drug Interactions of Selinexor with Posaconazole in Rats

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