Quantitative Determination of AZD3264, a Selective Ikb-Kinase IKK2 Inhibitor, in Dog Plasma by Solvent-Induced Phase Transition Extraction Coupled with HPLC-MS/MS and its Application to Pharmacokinetic Study in Dogs

2020 ◽  
Author(s):  
Gang Li ◽  
Shuofu Liang ◽  
Kesen Qiao ◽  
Chao Wang
Keyword(s):  
Phase Transition ◽  
Intravenous Administration ◽  
Internal Standard ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Studies ◽  
Preclinical Development ◽  
Bioanalytical Method Validation ◽  
Dog Plasma ◽  
Carry Over

Abstract Background AZD3264 is a small molecule inhibitor of selective IkB-kinase IKK2 currently in preclinical development for the potential treatment of asthma and chronic pulmonary obstructive disorder. Objective A method for the quantitative analysis of AZD3264 was established and optimized by using HPLC tandem mass spectrometry in dog plasma. Method Plasma samples were pretreated using a solvent-induced phase transition extraction method with a methanol solution of omeprazole as the internal standard. Chromatographic separation was performed using a Thermo Hypersil GOLD-C18 (50 mm × 4.6 mm, 3 μm) column with the temperature maintained at 25°C. Mobile phase consisted of 0.1% formic acid in water and acetonitrile in a gradient mode at a flow rate of 0.6 mL/min. Mass spectrometric detection was carried out in selected reaction monitoring mode with positive electrospray ionization, and the mass transitions of AZD3264 and omeprazole were m/z 442.1 → 425.0 and m/z 346.0 → 198.0, respectively. Results The intra-batch accuracy was within 95.11–105.06% and the precision was within 6.50–9.98%. The inter-batch accuracy was within 96.83–102.80% with a precision of 7.62–9.50%. The selectivity, sensitivity, linearity, dilution linearity, extraction recovery and matrix effect, stability, and carry-over met all requirements of the guidelines for bioanalytical method validation. AZD3264 showed linear pharmacokinetic characteristics following intravenous administration to dogs at 0.3–2.7 mg/kg. Conclusions The developed and validated method was successfully employed in pharmacokinetic studies in dogs following intravenous administration at the doses of 0.3, 0.9, and 2.7 mg/kg. Highlights This was the first investigation of the in vivo pharmacokinetic characteristics of AZD3264 in dogs by LC-MS/MS with SIPTE method for plasma sample preparation.

scholarly journals Pharmacokinetics and Tissue Distribution of Alnustone in Rats after Intravenous Administration by Liquid Chromatography-Mass Spectrometry

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3183 ◽  
Author(s):  
Yang Song ◽  
Yu Zhou ◽  
Xiao-Ting Yan ◽  
Jing-Bo Bi ◽  
Xin Qiu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Formic Acid ◽  
Tissue Distribution ◽  
Intravenous Administration ◽  
Peak Plasma ◽  
Internal Standard ◽  
Pharmacokinetic Studies ◽  
The Mean

Alnustone, a nonphenolic diarylheptanoid, first isolated from Alnus pendula (Betulaceae), has recently received a great deal of attention due to its various beneficial pharmacological effects. However, its pharmacokinetic profile in vivo remains unclear. The purpose of this study is to establish a fast and sensitive quantification method of alnustone using liquid chromatography tandem mass spectrometry (LC-MS/MS) and evaluate the pharmacokinetic and tissue distribution profiles of alnustone in rats. The sample was precipitated with acetonitrile with 0.5% formic acid and separated on BEH C18 Column. The mobile phase was composed of 0.1% formic acid in water and methanol at a flow rate of 0.3 mL/min. Alnustone and the internal standard (caffeine) were quantitatively monitored with precursor-to-product ion transitions of m/z 262.9→105.2 and m/z 195.2→138.0, respectively. The calibration curve for alnustone was linear from 1 to 2000 ng/mL. The intra- and inter-day assay precision (RSD) ranged from 1.1–9.0 % to 3.3–8.6%, respectively and the intra- and inter-day assay accuracy (RE) was between −8.2–9.7% and −10.3–9.9%, respectively. The validated method was successfully applied to the pharmacokinetic studies of alnustone in rats. After single-dose intravenous administration of alnustone (5 mg/kg), the mean peak plasma concentration (Cmax) value was 7066.36 ± 820.62 ng/mL, and the mean area under the concentration-time curve (AUC0–t) value was 6009.79 ± 567.30 ng/mL∙h. Our results demonstrated that the residence time of alnustone in vivo was not long and it eliminated quickly from the rat plasma. Meanwhile, the drug is mainly distributed in tissues with large blood flow, and the lung and liver might be the target organs for alnustone efficacy. The study will provide information for further application of alnustone.

Development and validation of a LC-MS/MS method for quantification of mobocertinib (TAK-788) in plasma and its application to pharmacokinetic study in rats

2020 ◽  
Vol 23 ◽  
Author(s):  
Bo Li ◽  
Jin Wang ◽  
Xinyao Dou ◽  
Xinjie Zhang ◽  
Xianbei Xue ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Kinase Inhibitor ◽  
Internal Standard ◽  
Selected Reaction Monitoring ◽  
Precipitation Method ◽  
Plasma Samples ◽  
Bioanalytical Method Validation ◽  
Extraction Recovery

Aim and Objective:: An analytical method for the determination of mobocertinib, an investigational tyrosine kinase inhibitor, was developed and optimized by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in rat plasma. Materials and Methods:: Plasma samples were pretreated by the protein precipitation method with a methanol solution of osimertinib as the internal standard (IS). Chromatographic separation was performed using an Inertsil ODS-3 column (50 mm × 4.6 mm, I.D. 5 μm) column with the temperature maintained at 40 °C. The mobile phase consisted of water (containing 0.1% formic acid) and methanol in a gradient mode at a flow rate of 0.5 mL/min. Mass spectrometric detection was carried out in the selected reaction monitoring (SRM) mode with positive electrospray ionization, and the mass transitions of mobocertinib and osimertinib were m/z 587.01 → 71.88 and m/z 499.80 → 71.94, respectively. The method was validated in terms of selectivity, linearity, accuracy and precision, extraction recovery and matrix effect, stability and carryover as per the guidelines for bioanalytical method validation (FDA, 2018). The method was applied to the pharmacokinetic study of mobocertinib in rats by oral gavage at the doses of 2, 6, and 18 mg/kg. A total of 216 plasma samples from 18 rats were analyzed. Results:: It showed good linearity over the range of 1-1000 ng/mL (R2 = 0.9957). The intra-batch accuracy was within 94.65-102.59% and the precision was within 5.49-10.46%. The inter-batch accuracy was within 97.08-102.25% with a precision of 7.54-10.13%. The extraction recovery and matrix factor were acceptable for the bioanalysis of mobocertinib. Additionally, mobocertinib was found to be stable under the detected conditions. Mobocertinib showed linear pharmacokinetic characteristics following oral administration to rats at 2.0-18.0 mg/kg. Conclusion:: The developed and validated method was successfully employed in the pharmacokinetic study in rats following oral administration of mobocertinib at the doses of 2, 6, and 18 mg/kg.

scholarly journals Development and Validation of a Method for Quantification of Favipiravir as COVID-19 Management in Spiked Human Plasma

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3789
Author(s):  
Mohammad Hailat ◽  
Israa Al-Ani ◽  
Mohammed Hamad ◽  
Zainab Zakareia ◽  
Wael Abu Dayyih
Keyword(s):  
Human Plasma ◽  
Internal Standard ◽  
Weighting Factor ◽  
Hplc Method ◽  
Bioanalytical Method Validation ◽  
Spiked Human Plasma ◽  
Fda Guidance ◽  
Significant Difference ◽  
Us Fda ◽  
Carry Over

In the current work, a simple, economical, accurate, and precise HPLC method with UV detection was developed to quantify Favipiravir (FVIR) in spiked human plasma using acyclovir (ACVR) as an internal standard in the COVID-19 pandemic time. Both FVIR and ACVR were well separated and resolved on the C18 column using the mobile phase blend of methanol:acetonitrile:20 mM phosphate buffer (pH 3.1) in an isocratic mode flow rate of 1 mL/min with a proportion of 30:10:60 %, v/v/v. The detector wavelength was set at 242 nm. Maximum recovery of FVIR and ACVR from plasma was obtained with dichloromethane (DCM) as extracting solvent. The calibration curve was found to be linear in the range of 3.1–60.0 µg/mL with regression coefficient (r2) = 0.9976. However, with acceptable r2, the calibration data’s heteroscedasticity was observed, which was further reduced using weighted linear regression with weighting factor 1/x. Finally, the method was validated concerning sensitivity, accuracy (Inter and Intraday’s % RE and RSD were 0.28, 0.65 and 1.00, 0.12 respectively), precision, recovery (89.99%, 89.09%, and 90.81% for LQC, MQC, and HQC, respectively), stability (% RSD for 30-day were 3.04 and 1.71 for LQC and HQC, respectively at −20 °C), and carry-over US-FDA guidance for Bioanalytical Method Validation for researchers in the COVID-19 pandemic crisis. Furthermore, there was no significant difference for selectivity when evaluated at LLOQ concentration of 3 µg/mL of FVIR and relative to the blank.

scholarly journals Simultaneous Determination of 5 Active Components of Periploca forrestii Schltr Extract in Rat Plasma by UPLC-MS and Its Application to Pharmacokinetic Studies in Normal and Adjuvant-Induced Arthritis Model Rats

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2098143
Author(s):  
Hui Liu ◽  
Hao Chen ◽  
Xiaoli Qin ◽  
Xue Ma ◽  
Zipeng Gong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chlorogenic Acid ◽  
Intravenous Administration ◽  
Area Under The Curve ◽  
Pharmacokinetic Studies ◽  
Active Components ◽  
Arthritis Model ◽  
Adjuvant Induced Arthritis ◽  
Neochlorogenic Acid

Periploca forrestii Schltr ( P. forrestii) is a herb used in traditional Chinese medicine for its anti-rheumatoid arthritis effect. The aim of this study was to compare the pharmacokinetic properties of the 5 active components of this plant: neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid C, and periplocin between normal rats and adjuvant-induced arthritis model rats. After the intravenous administration (177.78 mg/kg) of P. forrestii extract, samples were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Compared with normal rats, the area under the curve [(AUC)(0-t), AUC(0-∞)], mean residence time [(MRT)(0-t), MRT(0-∞)] of neochlorogenic acid-treated rats decreased significantly, and drug clearance (CL) and apparent volume of distribution (V) increased significantly; the V of chlorogenic acid-treated rats decreased significantly, and MRT(0-t) significantly increased; the AUC(0-t) and AUC(0-∞) of cryptochlorogenic acid-treated rats decreased significantly, and CL and V increased significantly; the AUC(0-t) and MRT(0-t) of isochlorogenic acid C-treated rats decreased significantly, and V increased significantly; the AUC(0-t) and AUC(0-∞) of periplocin-treated rats increased significantly, and MRT(0-t), MRT(0-∞), CL, and V decreased significantly in model rats. The disease condition of rheumatoid arthritis in rats had a significant effect on the in vivo pharmacokinetics of P. forrestii after the intravenous administration.

scholarly journals Quantification of Antimalarial Bisthiazolium Compounds and Their Neutral Bioprecursors in Plasma by Liquid Chromatography-Electrospray Mass Spectrometry

2005 ◽  
Vol 51 (3) ◽  
pp. 593-602 ◽  
Author(s):  
Olivier Nicolas ◽  
Christine Farenc ◽  
Michèle Calas ◽  
Henri J Vial ◽  
Françoise Bressolle
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Solid Phase ◽  
Internal Standard ◽  
Pharmacokinetic Studies ◽  
Ionization Mass ◽  
Limit Of Quantification ◽  
Lipophilic Prodrug

Abstract Background: A new class of antimalarial drugs targeting membrane biogenesis during intraerythrocytic Plasmodium falciparum development has been identified. The bisthiazolium salts T3 and T4 have superior in vitro and in vivo parasite-killing properties and need to be monitored. Methods: We used a liquid chromatography–electrospray ionization mass spectrometry method (positive mode) to quantify two bisthiazolium compounds (T3 and T4) and a related prodrug (TE4c) in human and rat plasma. Verapamil was used as internal standard. Verapamil and the TE4c compound were characterized by protonated molecules at m/z 455.7 and m/z 725.7, respectively. T3 and T4 were detected through two ions [M2+/2] at m/z 227.7 and m/z 241.8 and by their adducts with trifluoroacetic acid [M+TFA]+ at m/z 568 and m/z 596, respectively. The sample clean-up procedure involved solid-phase extraction. HPLC separation was performed on a reversed-phase column, using a water–acetonitrile gradient, with both solvents containing TFA. Stability under various conditions was also investigated. Results: The peak-area ratios (drugs/internal standard) were linked to concentrations (6.4–1282 μg/L for T3; 6.5–1309.8 μg/L for T4; 20–2000 μg/L for TE4c) according to a quadratic equation. The accuracy ranged from 85% to 113.1%, and the imprecision from 2.2% to 15%. The mean extraction recoveries were 87%, 98%, and 80% for T3, T4, and TE4c, respectively. The lower limit of quantification was 6.4 μg/L for the two bisthiazolium compounds, whereas it was 20 μg/L for TE4c, the related lipophilic prodrug. Conclusion: This highly specific and sensitive method is suitable for analyzing samples collected during preclinical pharmacokinetic studies in rats and to determine the percentage binding of T3 and T4 to human plasma proteins.

scholarly journals Pharmacokinetics, Bioavailability, Excretion and Metabolism Studies of Akebia Saponin D in Rats: Causes of the Ultra-Low Oral Bioavailability and Metabolic Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Pengfei Li ◽  
Jun Peng ◽  
Yuexin Li ◽  
Lili Gong ◽  
Yali Lv ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Intravenous Administration ◽  
Oral Bioavailability ◽  
Biological Activities ◽  
Intestinal Flora ◽  
Internal Standard ◽  
Terminal Phase ◽  
Lipid Solubility ◽  
Gastrointestinal Permeability

Background: Akebia saponin D (ASD) has a variety of biological activities and great medicinal potential, but its oral bioavailability is so low as to limit its development. Its pharmacokinetic profiles and excretion and metabolism in vivo have not been fully elucidated. This study was an attempt in this area.Methods: A simple LC-MS/MS method to simultaneously quantify ASD and its metabolites M1∼M5 in rat plasma, feces, urine and bile was established with a negative ESI model using dexketoprofen as the internal standard. Meanwhile, the UPLC-HR/MS system was used to screen all possible metabolites in the urine, feces and bile of rats, as compared with blank samples collected before administration. Absolute quantitative analysis was for M0, M3, M4, and M5, while semi-quantitative analysis was for M1, M2, and Orbitrap data.Results: The AUC0-t values after intravenous administration of 10 mg/kg and intragastrical administration of 100 mg/kg ASD were 19.05 ± 8.64 and 0.047 ± 0.030 h*μg/ml respectively. The oral bioavailability was determined to be extremely low (0.025%) in rats. The exposure of M4 and M5 in the oral group was higher than that of M0 in the terminal phase of the plasma concentration time profile, and ASD was stable in the liver microsome incubation system of rats, but metabolism was relatively rapid during anaerobic incubation of intestinal contents of rats, suggesting that the low bioavailability of ASD might have been attributed to the poor gastrointestinal permeability and extensive pre-absorption degradation rather than to the potent first pass metabolism. This assertion was further verified by a series of intervention studies, where improvement of lipid solubility and intestinal permeability as well as inhibition of intestinal flora increased the relative bioavailability to different extents without being changed by P-gp inhibition. After intravenous administration, the cumulative excretion rates of ASD in the urine and bile were 14.79 ± 1.87%, and 21.76 ± 17.61% respectively, but only 0.011% in feces, suggesting that the urine and bile were the main excretion pathways and that there was a large amount of biotransformation in the gastrointestinal tract. Fifteen possible metabolites were observed in the urine, feces and bile. The main metabolites were ASD deglycosylation, demethylation, dehydroxylation, decarbonylation, decarboxylation, hydroxylation, hydroxymethylation, hydroxyethylation and hydrolysis.Conclusion: The pharmacokinetics, bioavailability, metabolism and excretion of ASD in rats were systematically evaluated for the first time in this study. It has been confirmed that the ultra-low oral bioavailability is due to poor gastrointestinal permeability, extensive pre-absorption degradation and biotransformation. ASD after iv administration is not only excreted by the urine and bile, but possibly undergoes complex metabolic elimination.

scholarly journals Metabolite identification, tissue distribution, excretion and preclinical pharmacokinetic studies of ET-26-HCl, a new analogue of etomidate

2020 ◽  
Vol 7 (2) ◽  
pp. 191666
Author(s):  
Lu Yu ◽  
Xu Chen ◽  
Wen Sheng Zhang ◽  
Liang Zheng ◽  
Wen Wen Xu ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Intravenous Administration ◽  
High Performance ◽  
Anaesthetic Agent ◽  
Parent Compound ◽  
Liver Microsomes ◽  
Metabolite Identification ◽  
Pharmacokinetic Studies

ET-26-HCl, a novel anaesthetic agent with promising pharmacological properties, lacks extensive studies on pharmacokinetics and disposition in vitro and in vivo . In this study, we investigated the metabolic stability, metabolite production and plasma protein binding (PPB) of ET-26-HCl along with its tissue distribution, excretion and pharmacokinetics in animals after intravenous administration. Ultra-high performance liquid chromatography–tandem quadrupole time-of-flight mass spectrometry identified a total of eight new metabolites after ET-26-HCl biotransformation in liver microsomes from different species. A hypothetical cytochrome P450-metabolic pathway including dehydrogenation, hydroxylation and demethylation was proposed. The PPB rate was highest in mouse and lowest in human. After intravenous administration, ET-26-HCl distributed rapidly to all tissues in rats and beagle dogs, with the highest concentrations in fat and liver. High concentrations of ET-26-acid, a major hydroxylation metabolite of ET-26-HCl, were found in liver, plasma and kidney. Almost complete clearance of ET-26-HCl from plasma occurred within 4 h after administration. Only a small fraction of the parent compound and its acid form were excreted via the urine and faeces. Taken together, the results added to a better understanding of the metabolic and pharmacokinetic properties of ET-26-HCl, which may contribute to the further development of this drug.

scholarly journals Quantitation of Apremilast in Beagle Dogs Plasma by UPLC-MS-MS and Its Application to Pharmacokinetic Studies

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Wei Xiong ◽  
Ling Wang ◽  
Haiyan Zhang ◽  
Xiaoqiu Tao ◽  
Xuehua Jiang ◽  
...  
Keyword(s):  
Internal Standard ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Ammonium Formate ◽  
Pharmacokinetic Studies ◽  
Beagle Dogs ◽  
Beagle Dog ◽  
Dog Plasma ◽  
Liquid Chromatography Tandem Mass

A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of apremilast in beagle dog plasma has been developed and successfully validated in the current study. Clopidogrel was employed as an internal standard (IS), and liquid-liquid extraction by tert-butylmethyl ether was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH Shield RP18 column (50 mm × 2.1 mm, 1.7 μm) with 5 mM ammonium formate water and 5 mM ammonium formate methanol as the mobile phase with gradient elution. Calibration plots were linear in the range of 2–3000 ng/mL for apremilast in beagle dog plasma. Mean recoveries of apremilast in beagle dogs plasma ranged from 87.4% to 97.4%. The intrarun and interrun precision was less than 6% and 9%, respectively, with the accuracy between 92.4% and 101.1%. The method has also been successfully applied in the pharmacokinetics study of apremilast. The mean t1/2Z was 5.41 h for 30 mg·day−1 for beagle dogs after oral administration. The AUC0-t increased linearly from 3.51 to 1802.13  μ g   L − 1 ∗ h after administration of single doses.

scholarly journals Investigation of In Vivo and In Vitro Pharmacokinetic Characteristics of Kaji-ichigoside F1 in Rats

2020 ◽  
Vol 15 (3) ◽  
pp. 1934578X2091501
Author(s):  
Wenjuan Cui ◽  
Xiaoguang Fan ◽  
Naizhi Wang ◽  
Zhikun Zhang ◽  
Zhaolong Zhang ◽  
...  
Keyword(s):  
High Performance ◽  
Single Step ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Studies ◽  
Triterpenoid Saponin ◽  
Pentacyclic Triterpenoid ◽  
Validation Parameters ◽  
Liquid Chromatography Tandem Mass

Kaji-ichigoside F1, a pentacyclic triterpenoid saponin, exhibits various beneficial pharmacological effects. In this study, a simple, rapid, and specific high-performance liquid chromatography-tandem mass spectrometry method for rapid quantification of kaji-ichigoside F1 in rat biological matrix was developed. Plasma was prepared by a single-step protein precipitation followed by separation of the analyte using an Inertsil ODS-3 column with a gradient mobile phase. Positive ion electrospray was used and selected reaction monitoring transitions were m/ z 673.27 → 511.15 for kaji-ichigoside F1 and m/ z 429.19 → 267.29 for morroniside, respectively. The developed method was validated with linear range of 20 to 10 000 ng/mL. All validation parameters were well within the acceptance limit based on the guidance of FDA. The validated method was successfully applied to analyze samples from the in vivo and in vitro pharmacokinetic studies in rats.

scholarly journals Simultaneous Determination of Docetaxel and Celecoxib in Porous Microparticles and Rat Plasma by Liquid-Liquid Extraction and HPLC with UV Detection: in vitro and in vivo Validation and Application

2020 ◽  
Vol 23 ◽  
pp. 289-303
Author(s):  
Elham Ziaei ◽  
Jaber Emami ◽  
Moloud Kazemi ◽  
Mahboubeh Rezazadeh
Keyword(s):  
Internal Standard ◽  
Rat Plasma ◽  
Liquid Extraction ◽  
Uv Detection ◽  
Pharmacokinetic Studies ◽  
Liquid Liquid Extraction ◽  
Porous Microparticles ◽  
Limit Of Quantitation

Purpose: A simple, rapid, sensitive, and reliable HPLC method with UV detection was developed and validated for simultaneous quantitation of docetaxel and celecoxib and paclitaxel for dissolution characterization and pharmacokinetic studies. Methods: The HPLC assay was performed isocratically on a reversed-phase C18 μ-Bondapack column using a mobile phase of acetonitrile:water (45:55, v/v) at a flow rate of 1.2 mL/min, and the analytes were detected at 230 nm. Paclitaxel was used as an internal standard for analysis of plasma samples following simple liquid-liquid extraction with n-hexane:isoamyl alcohol (97:3). The method was validated for specificity, linearity, sensitivity, precision, accuracy, robustness, and in vitro-in vivo application. Results: The retention times for docetaxel, paclitaxel, and celecoxib were 10.94, 12.4, and 16.81 min, respectively. The standard curves covering 0.1-1 μg/mL and 0.05-4 μg/mL were linear using dissolution medium and rat plasma, respectively. The limit of quantitation of the method was 50 ng/mL using 100 μL of rat plasma sample and injection of 50 μL of the residue. Within- and between-day precision and accuracy did not exceed 16.86% and 12.10%, respectively. This validated method was successfully used to quantify docetaxel and celecoxib simultaneously in the release study of docetaxel-celecoxib -loaded porous microparticles and pharmacokinetics studies. The methods were found to be simple, specific, precise, accurate, and reproducible. In this study, paclitaxel was used as the internal standard while dexamethasone, flutamide, and budesonide proved suitable alternative as an internal standard. Conclusion: Since docetaxel and celecoxib could be co-administered for the treatment of a wide range of cancers such as non-small cell lung carcinoma, the developed method is particularly advantageous for routine therapeutic drug monitoring and pharmacokinetic studies of these drugs.

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