Ultrasound-guided anterior quadratus lumborum block at the L2 level for postsurgical analgesia in patients undergoing laparoscopic gynaecological surgery: a single-centre, randomised, double-blinded trial at a university-affiliated hospital in China.

OBJECTIVE: This study aimed to investigate the analgesic effect of an ultrasound-guided anterior quadratus lumborum block (QLB) at the L2 level on postoperative pain after laparoscopic gynaecological surgery. DESIGN: Prospective single-centre randomised double-blind trial. SETTING: University-affiliated hospital. PARTICIPANTS: Sixty patients aged between 18 and 65 years scheduled for laparoscopic gynaecological surgery. INTERVENTIONS: Before surgery, bilateral anterior QLB was performed with 20 mL of 0.375% ropivacaine injected on each side in the QLB group, whereas equal amount of saline was administered in the placebo group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the cumulative morphine dose in the first 24 hours, and the secondary endpoints were morphine consumption at each time interval, area under the curve (AUC) of the numeric rating scale (NRS) for pain, maximum pain intensity, incidence of moderate-to-severe pain (NRS>3), sedation score, adverse events, and time to home-readiness. RESULTS: Cumulative morphine consumption in the first 24 hours after surgery was significantly lower in the QLB group than in the placebo group (mean difference, 14.2; 95% CI 6.3 to 22.1; p<0.001). The AUCs of NRS pain intensity scores, including visceral and incisional pain at rest and on movement, were significantly lower in the QLB group than in the placebo group (all p<0.001). The time to home-readiness was significantly shorter in the QLB group than in the placebo group (p<0.05). CONCLUSION: Ultrasound-guided anterior QLB at the L2 level significantly reduced morphine consumption and relieved visceral and incision pain intensity after laparoscopic gynaecological surgery, which was beneficial for enhanced recovery. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-IOR-17011960).

Role of galectin-3 in vascular calcification.

Vascular calcification is an abnormal process in which bone specific hydroxyapatite crystals are actively deposited on the vascular wall mediated by phenotypic differentiated smooth muscle cells and other mesenchymal cells under various pathological conditions. It is one of the important characteristics in the occurrence and development of atherosclerosis, prevalent in patients with type 2 diabetes and advanced chronic kidney disease, especially those requiring maintenance hemodialysis, with severely threatening human health. Previous studies have shown that the early diagnosis and control of vascular calcification is of great significance for cardiovascular risk stratification, prevention of acute cardiovascular events, which can greatly improve the prognosis and quality of life of patients. Galectins are a family of lectin superfamily. It is widely distributed in various animals and plays an important role in many physiological and pathological processes, such as cell adhesion, apoptosis, inflammatory response, tumor metastasis and so on. Many biomarker-and association-related studies and Preclinical-mechanistic studies have suggested that galactose-specific lectin-3 (galectin-3) plays an important role in vascular calcification and vascular intimal calcification (VIC) calcification induced by Wnt/ßcatenin signaling pathway, NF-κB signaling pathway and ERK1/2 signaling pathway. This paper mainly expounds the role and mechanism of galectin-3 in vascular calcification under different pathological conditions including atherosclerosis, diabetes and chronic kidney disease.

The utility of a multi-orifice epidural catheter when using the "Spray-as-You-Go" technique for topical Airway Anesthesia during Flexible Bronchoscopy, a randomised trial.

BACKGROUND: Lidocaine administered through the working channel of a flexible bronchoscope can provide effective local anesthesia but cannot achieve good distribution in the airway. This study was undertaken to determine whether lidocaine delivered via a multi-orifice epidural catheter (three orifices/openings) is superior to conventional method and if a better distribution and decreased the cough reflex can be achieved. METHODS: The patients (N = 100; 50 in each group) were randomized to receive either topical airway anesthesia by the "spray-as-you-go" technique via conventional application (group C) through the working channel of the bronchoscope or via a triple-orifice epidural catheter (group E). The primary outcome measurement was the cough severity, which was documented using a 4-point scale. Bronchoscopists and nurses assessed the coughing. The visual analogue scale (VAS) score for cough, total consumption of propofol and lidocaine, requirement frequency of propofol and topical anesthesia, PACU retention time, and adverse events were also compared. RESULTS: There was a significant difference in the median cough severity scores between the two groups (group C: 3 vs. group E: 2, P = 0.004). The median visual analogue scale (VAS) scores for the cough, were significantly higher in group C than those in group E (bronchoscopist: 3 vs. 2 P = 0.002; nurse: 3 vs. 2, P < 0.001). The incidence of cough was significantly higher in group C in the trachea, left and right bronchi. The highest respiratory rate was higher in group C than in group E (P < 0.01). Eight patients in group C and two patients in group E had an oxygen saturation below 90% during flexible bronchoscopy(FB) (P = 0.046). More patients in group C required extra topical anesthesia than in group E (P < 0.001). The total lidocaine consumption was also higher in group C than that in group E (P < 0.001). CONCLUSIONS: Endotracheal topical anesthesia via the multi-orifice epidural catheter (three holes/openings) during flexible bronchoscopy using the "spray-as-you-go" technique was appeared to be superior to the conventional method.

Anterior Quadratus Lumborum block area comparison in the three different volumes of Ropivacaine: a double-blind, randomized controlled trial in healthy volunteers.

BACKGROUND: In abdominal surgery, ultrasound-guided anterior quadratus lumborum blocks (QLB) are performed to induce analgesia. However, no study reported suitable volumes of the anterior QLB for the different postoperative analgesia regions. Therefore, this prospective randomized controlled study assessed the dermatomal spread and analgesic effects of the three different volumes of a local anesthetic for anterior QLB. METHODS: Ultrasound-guided anterior QLB was performed at the L2 level on 30 healthy volunteers. The volunteers were randomized to receive 20 ml (n = 10), 30 ml (n = 10), and 40 mL (n = 10) of 0.375% ropivacaine. The cutaneous sensory blocked area (CSBA), the number of block dermatomes, and the block duration time were measured by determining the extent of the cold sensation. RESULTS: The CSBA was significantly larger in the 40 ml group than in the 30 (P = 0.001; 1350.6 ± 234.4 vs. 1009.5 ± 151.6 cm2) and 20 ml groups (P < 0.001; 1350.6 ± 234.4 vs. 808.1 ± 120.5 cm2). Similarly, the number of blocked dermatomes was significantly higher in the 40 ml group than in the 30- and 20-ml groups. However, no significant difference was observed in block duration among the groups. CONCLUSIONS: No difference was observed in block duration with the various volumes of 0.375% ropivacaine. However, the larger volume for anterior QLB contributed to a larger area of cutaneous sensory blockade. Appropriate volumes in anterior QLB can create suitable postoperative analgesia levels for the different operative sites. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registration Center on www.chictr.org.cn on 27th April 2018 (registration number: ChiCTR-IOR-17010853).

The difference of gut microbiome in different biliary diseases in infant before operation and the changes after operation.

BACKGROUND: Evidence supports an association between cholestatic liver disease and changes in microbiome composition. Nevertheless, the identification of this special type of biliary atresia from non-biliary atresia cholestasis is still a major clinical difficulty. The purpose of this study is to compare the differences in the composition of gut microbiome between infants with biliary atresia and infant with non-biliary atrestic cholestasis, to find new ways to identify and diagnose these two diseases early, to understand the influence of the presence or absence of bile on the composition of the gut microbiome in infants with cholestasis. METHODS: Using 16S rDNA gene sequencing technology to analyze the intestinal flora of the participants. RESULTS: In terms of diversity, there is an obvious structural separation in the intestinal microbiota of the BA group and the CD group, and this structural separation also exists in the comparison between the two groups before surgery. Taxonomic analysis demonstrated that the two groups showed an increase in Proteobacteria and Firmicutes before surgery, and the relative abundance of potential pathogens such as Shigella, Streptococcus, Klebsiella, etc. increased, potential probiotics such as Bifidobacteria and Lactobacillus decreased, but the relative abundance of each genus was different between groups. It was found that Enterococcus, Ralstonia, Nitriliruptoraceae, etc. were differentially enriched in the BA group, the CD group are mainly enriched in Veillonella, Clostridium_sensu_stricto_1 and Lactobacillus. Functional analysis of the groups showed that the BA group mainly focused on the processes of energy release processes, and the CD group mainly focused on the biosynthesis of amino-acids to consume energy. CONCLUSIONS: The composition of intestinal flora is different between biliary atresia and non-biliary atretic cholestasis. Enterococcus, Ralstonia, etc. may become biomarkers for the identification and diagnosis of both.

Polyphyllin I alleviates inflammatory injury in mice with gestational diabetes through AMPK pathway.

Our study aimed to detect the effects of polyphyllin I (PPI) on relieving gestational diabetes mellitus (GDM), and the possible mechanism. A mouse model of GDM was constructed. The effects of PPI on GDM mice were evaluated by detecting blood glucose, insulin level, glucose tolerance test, and insulin tolerance test. The inflammation response in GDM and GDM+PPI group were evaluated by enzyme-linked immunosorbent assay (ELISA). The effect of PPI on the offspring of GDM mice was analyzed. In addition, immunoblot assays were performed to investigate the effects of PPI on the AMPK pathway. We found that PPI improved diabetes-related symptoms and decreased serum inflammatory response in GDM mice. In addition, we also found that PPI reduced the tissue damage of GDM mice. We noticed that PPI alleviated inflammatory injury in GDM mice through targeting AMPK pathway. Our findings showed that PPI has the potential to be explored as the drug for GDM treatment.

Apelin-13 Reverses Bupivacaine-Induced Cardiotoxicity via the Adenosine Monophosphate-Activated Protein Kinase Pathway.

BACKGROUND: Cardiotoxicity can be induced by the commonly used amide local anesthetic, bupivacaine. Bupivacaine can inhibit protein kinase B (AKT) phosphorylation and activated adenosine monophosphate-activated protein kinase alpha (AMPKα). It can decouple mitochondrial oxidative phosphorylation and enhance reactive oxygen species (ROS) production. Apelin enhances the phosphatidylinositol 3-kinase (PI3K)/AKT and AMPK/acetyl-CoA carboxylase (ACC) pathways, promotes the complete fatty acid oxidation in the heart, and reduces the release of ROS. In this study, we examined whether exogenous (Pyr1) apelin-13 could reverse bupivacaine-induced cardiotoxicity. METHODS: We used the bupivacaine-induced inhibition model in adult male Sprague Dawley (SD) rats (n = 48) and H9c2 cardiomyocyte cell cultures to explore the role of apelin-13 in the reversal of bupivacaine cardiotoxicity, and its possible mechanism of action. AMPKα, ACC, carnitine palmitoyl transferase (CPT), PI3K, AKT, superoxide dismutase 1 (SOD1), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47-phox) were quantified. Changes in mitochondrial ultrastructure were examined, and mitochondrial DNA, cell viability, ROS release, oxygen consumption rate (OCR) were determined. RESULTS: Apelin-13 reduced bupivacaine-induced mitochondrial DNA lesions in SD rats (P < .001), while increasing the expression of AMPKα (P = .007) and PI3K (P = .002). Furthermore, apelin-13 blocked bupivacaine-induced depolarization of the mitochondrial membrane potential (P = .019) and the bupivacaine-induced increases in ROS (P = .001). Also, the AMPK pathway was activated by bupivacaine as well as apelin-13 (P = .002) in H9c2 cardiomyocytes. Additionally, the reduction in the PI3K expression by bupivacaine was mitigated by apelin-13 in H9c2 cardiomyocytes (P = .001). While the aforementioned changes induced by bupivacaine were not abated by apelin-13 after pretreatment with AMPK inhibitor compound C; the bupivacaine-induced changes were still mitigated by apelin-13, even when pretreated with PI3K inhibitor-LY294002. CONCLUSIONS: Apelin-13 treatment reduced bupivacaine-induced oxidative stress, attenuated mitochondrial morphological changes and mitochondrial DNA damage, enhanced mitochondrial energy metabolism, and ultimately reversed bupivacaine-induced cardiotoxicity. Our results suggest a role for the AMPK in apelin-13 reversal of bupivacaine-induced cardiotoxicity.

Dexmedetomidine preconditioning ameliorates lung injury induced by pulmonary ischemia/reperfusion by upregulating promoter histone H3K4me3 modification of KGF-2.

Keratinocyte growth factor (KGF)-2 has been highlighted to play a significant role in maintaining the endothelial barrier integrity in lung injury induced by ischemia-reperfusion (I/R). However, the underlying mechanism remains largely unknown. The aims of this study were to determine whether dexmedetomidine preconditioning (DexP) modulates pulmonary I/R-induced lung injury through the alteration in KGF-2 expression. In our I/R-modeled mice, DexP significantly inhibited pathological injury, inflammatory response, and inflammatory cell infiltration, while promoted endothelial barrier integrity and KGF-2 promoter activity in lung tissues. Bioinformatics prediction and ChIP-seq revealed that I/R significantly diminished the level of H3K4me3 modification in the KGF-2 promoter, which was significantly reversed by DexP. Moreover, DexP inhibited the expression of histone demethylase JMJD3, which in turn promoted the expression of KGF-2. In addition, overexpression of JMJD3 weakened the protective effect of DexP on lung injury in mice with I/R. Collectively, the present results demonstrated that DexP ameliorates endothelial barrier dysfunction via the JMJD3/KGF-2 axis.

Single and Repeated Intrapleural Ropivacaine Administration: A Plasma Concentration and Pharmacodynamics Study.

BACKGROUND: Intrapleural analgesia has been increasingly recommended for postoperative analgesia after thoracic surgery. However, the analgesic effect provided by a single intrapleural administration is time limited. This study reports the efficacy and safety of repeated intrapleural 0.75% ropivacaine administration after thoracoscopic surgery. METHODS: Twenty patients were randomly divided into two groups: a single administration group receiving a single intrapleural injection of 0.75% ropivacaine 15 mL (single administration group, SA group), and a repeated administration group with an intrapleural injection of 0.75% ropivacaine 15 mL every 4h for 4 doses (repeated administration group, RA group). The primary outcomes of this study were the peak plasma concentration of ropivacaine and 24h morphine consumption. The secondary outcomes were pain score, patient satisfaction, extubation time, hospital length of stay, and adverse reactions. RESULTS: In SA group, the highest plasma concentration after intrapleural administration of 0.75% ropivacaine 15 mL was 1345±364 µg/L. The highest plasma concentration in RA group after the fourth administration was 1864±492 µg/L. The 24h morphine consumption in RA group was significantly less than that in SA group (9.0±5.66 vs 15.9±3.48 mg, P=0.004). The NRS scores at rest and while coughing of patients in RA group were significantly lower than those in SA group at 5, 9, 13, 17 and 24h after operation. The patients in RA group had higher satisfaction than those in SA group. There was no significant difference in postoperative adverse events, drainage tube placement days and hospital length of stay between the two groups. CONCLUSION: Repeated intrapleural administration with 0.75% ropivacaine, 15 mL every 4h for 4 doses after video-assisted thoracoscopic lobectomies, can provide a more durable and more effective analgesic effect than single intrapleural administration. Repeated intrapleural administration of ropivacaine is an effective postoperative method of analgesia resulting in higher patient satisfaction. Moreover, it was also able to keep the plasma concentration of ropivacaine within a possible safe range. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17010560.

Role of PI3K in the Progression and Regression of Atherosclerosis.

Phosphatidylinositol 3 kinase (PI3K) is a key molecule in the initiation of signal transduction pathways after the binding of extracellular signals to cell surface receptors. An intracellular kinase, PI3K activates multiple intracellular signaling pathways that affect cell growth, proliferation, migration, secretion, differentiation, transcription and translation. Dysregulation of PI3K activity, and as aberrant PI3K signaling, lead to a broad range of human diseases, such as cancer, immune disorders, diabetes, and cardiovascular diseases. A growing number of studies have shown that PI3K and its signaling pathways play key roles in the pathophysiological process of atherosclerosis. Furthermore, drugs targeting PI3K and its related signaling pathways are promising treatments for atherosclerosis. Therefore, we have reviewed how PI3K, an important regulatory factor, mediates the development of atherosclerosis and how targeting PI3K can be used to prevent and treat atherosclerosis.

Omentin-1 attenuates glucocorticoid-induced cardiac injury by phosphorylating GSK3ß.

Glucocorticoid excess often causes a variety of cardiovascular complications, including hypertension, atherosclerosis, and cardiac hypertrophy. To abrogate its cardiac side effects, it is necessary to fully disclose the pathophysiological role of glucocorticoid in cardiac remodelling. Previous clinical and experimental studies have found that omentin-1, one of the adipokines, has beneficial effects in cardiovascular diseases, and is closely associated with metabolic disorders. However, there is no evidence to address the potential role of omentin-1 in glucocorticoid excess-induced cardiac injuries. To uncover the links, the present study utilized rat model with glucocorticoid-induced cardiac injuries and clinical patients with abnormal cardiac function. Chronic administration of glucocorticoid excess reduced rat serum omentin-1 concentration, which closely correlated with cardiac functional parameters. Intravenous administration of adeno-associated virus encoding omentin-1 upregulated the circulating omentin-1 level and attenuated glucocorticoid excess-induced cardiac hypertrophy and functional disorders. Overexpression of omentin-1 also improved cardiac mitochondrial function, including the reduction of lipid deposits, induction of mitochondrial biogenesis, and enhanced mitochondrial activities. Mechanistically, omentin-1 phosphorylated and activated the GSK3ß pathway in the heart. From a study of 28 patients with Cushing's syndrome and 23 healthy subjects, the plasma level of glucocorticoid was negatively correlated with omentin-1, and was positively associated with cardiac ejection fraction and fractional shortening. Collectively, the present study provided a novel role of omentin-1 in glucocorticoid excess-induced cardiac injuries and found that the omentin-1/GSK3ß pathway was a potential therapeutic target in combating the side effects of glucocorticoid.

Ganoderic acid A attenuates high-fat-diet-induced liver injury in rats by regulating the lipid oxidation and liver inflammation.

Ganoderic Acid A (GA) has many pharmacological effects such as anti-tumor, antibacterial, anti-inflammatory, and immunosuppressive effects. However, the protective effect of GA on liver injury has not been reported. This study aimed to investigate the action of GA on insufficient methionine and choline combined with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats. NAFLD model was established by insufficient methionine and choline combined with high fat feeding to rats. The levels of Acetyl-CoA carboxylase, fatty acid synthase, sterol regulatory element binding protein, liver X receptors, AMP-activated protein kinase, peroxisome proliferator-activated receptor α, PPARg coactivator 1α and NF-κB pathway in the liver were detected by western blot. The results of this study demonstrated that the expression of GA can not only significantly decrease the live weight and liver weight per body weight of HFD mice, but also restore the alanine aminotransferase, aspartate aminotransferase, total bilirubin levels, triglyceride and cholesterol in serum. In addition, the expression of GA increased the levels of high-density lipoprotein cholesterol in serum, ameliorated pathological changes and decreased NAS score of mice's liver. In conclusion, the treatment with GA could improve NAFLD in rats by regulating the levels of signaling events involved in free fatty acid production, lipid oxidation and liver inflammation.

Tetramerized Sesquiterpenoid Ainsliatetramers A and B from Ainsliaea fragrans and Their Cytotoxic Activities.

Two guaianolide sesquiterpenoid tetramers named ainsliatetramers A and B were separated from Ainsliaea fragrans. Through spectroscopic analyses, especially the band-selective CT-HSQC and CT-HMBC techniques, the complex skeleton was constructed from four sesquiterpene units via three different linkages. A biosynthetic pathway was proposed featuring a Michael addition and a regular and a hetero-Diels-Alder cycloaddition. Both exhibited potent cytotoxicity against human cancer cell lines with IC50 values ranging from 2 to 15 µM.

Comparison of programmed intermittent bolus infusion and continuous infusion for postoperative patient-controlled analgesia with thoracic paravertebral block catheter: a randomized, double-blind, controlled trial.

BACKGROUND AND OBJECTIVES: In this randomized, double-blind, controlled study, we hypothesized that programmed intermittent bolus infusion (PIBI) of local anesthetic for continuous paravertebral block (PVB), combined with patient-controlled analgesia (PCA), provided better pain control, better patient satisfaction, and decreased in local anesthetic consumption when compared with a continuous infusion (CI) combined with PCA, after video-assisted thoracoscopic unilateral lung resection surgery. METHODS: Preoperatively, patients undergoing video-assisted thoracoscopic unilateral lung resection surgery received ipsilateral paravertebral catheters inserted at the level of thoracic vertebrae 4 and 5. All the subjects received an initial bolus of 15 mL 0.375% ropivacaine via the catheters. Subjects were randomized to receive 0.2 % ropivacaine 8 mL/h as either PIBI (n=17) or CI (n=17) combined with a PCA pump. The pain scores, frequency of PCA, local anesthetic consumption, patient satisfaction, and the need for rescue analgesia with tramadol were recorded until 48 hours postoperative. RESULTS: The numeric rating scale scores in the PIBI group were significantly lower than the CI group at 4, 8, 12 hours and 4, 8, 12, 24 hours postoperatively, at rest, and during coughing, respectively. PCA local anesthetic consumption (30 mg (20-60 mg) vs 120 mg (70-155 mg), p=0.000) and frequency of PCA use over 48 hours (3 (2-6) vs 12 (7-15.5), p=0.000) was lower in the PIBI group as compared with the CI group. Additionally, the PIBI group showed greater patient satisfaction. The need for tramadol rescue was similar in the two groups. CONCLUSIONS: In PVBs, local anesthetic administered as a PIBI in conjunction with PCA provided superior postoperative analgesia to a CI combined with PCA in patients undergoing video-assisted thoracoscopic unilateral lung resection surgery. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-17011253.

The ED95 of Nalbuphine in Outpatient-Induced Abortion Compared to Equivalent Sufentanil.

This prospective study evaluated the 95% effective dose (ED95 ) of nalbuphine in inhibiting body movement during outpatient-induced abortion and its clinical efficacy versus the equivalent of sufentanil. The study was divided into two parts. For the first part, voluntary first-trimester patients who needed induced abortions were recruited to measure the ED95 of nalbuphine in inhibiting body movement during induced abortion using the sequential method (the Dixon up-and-down method). In the second part, this was a double-blind, randomized study. Sixty cases of first-trimester patients were recruited and were randomly divided into two groups (n = 30), including group N (nalbuphine at the ED95 dose) and group S (sufentanil at an equivalent dose). Propofol was given to both groups as the sedative. The circulation, respiration and body movement of the two groups in surgery were observed. The amount of propofol, the awakening time, the time to leave the hospital and the analgesic effect were recorded. The ED95 of nalbuphine in inhibiting body movement during painless surgical abortion was 0.128 mg/kg (95% confidence intervals 0.098-0.483 mg/kg). Both nalbuphine and the equivalent dose of sufentanil provided a good intraoperative and post-operative analgesic effect in outpatient-induced abortion. However, the post-operative morbidity of dizziness for nalbuphine was less than for sufentanil (p < 0.05), and the awakening time and the time to leave the hospital were significantly shorter than those of sufentanil (p < 0.05). Nalbuphine at 0.128 mg/kg was used in outpatient-induced abortion as an intraoperative and post-operative analgesic and showed a better effect compared with sufentanil.

A reliable and stable method for determination of brigatinib in rat plasma by UPLC-MS/MS: Application to a pharmacokinetic study.

Brigatinib is the second-generation anaplastic lymphoma kinase - inhibitor in non-small cell lung cancer and it can overcome the crizotinib-resistance. Chromatographic separation was carried out on an Acquity Ultra Performance Liquid Chromatography (UPLC) unit with a BEH C18 column (2.1mm×50mm, 1.7µm). The mobile phase was composed of acetonitrile and 0.1% formic acid in water. No endogenous interfering compounds was discovered at retention time of brigatinib (0.56min) and imatinib (IS, 1.41min). MS/MS detection was performed in positive mode. And the MRM transitions were m/z 584.09→484.08 and m/z 494.3→394.2 for brigatinib and IS, respectively. This method was assessed to be stable, specificity, and no matrix effect in three concentrations (0.004, 0.4, 4µg/mL). The intra-day and inter-day precisions were less than 11.09% and 6.43%. And intra-day and inter-day accuracies were ranged from -3.88% to 5.44%. The recovery of brigatinib was from 85.26% to 96.05%. Additionally, the method had a good linearity in the range of 0.002-5µg/mL. The presented method was effectively implemented to determine the concentration of brigatinib in rat plasma.