In the current research experiment, a sensitive, precise and rapid bioanalytical approach involving the detection of fedratinib concentrations in rat plasma by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was optimized and established, and it was employed to describe the changes of fedratinib concentrations after oral treatment with various antifungal drugs (isavuconazole, posaconazole, fluconazole and itraconazole). An Acquity UPLC BEH reverse-phase C18 column (2.1 mm × 50 mm, 1.7 μm) was used for chromatographic separation of fedratinib and bosutinib (as internal standard (IS) in our study) under a linear gradient elution of the mobile phase, which was composed of solution A (acetonitrile) and solution B (water with 0.1% formic acid), along with 0.40 ml/min flow rate. The analyte and internal standard were measured with electrospray ion source in positive ion mode on a XEVO TQS triple quadrupole tandem mass spectrometer. The newly developed UPLC-MS/MS assay displayed enough linearity within the concentration range of 0.5–500 ng/ml for calibration curve. The intra- and inter-day of precision and accuracy were evaluated and validated to meet the requirements for the guidelines of bioanalytical assay. In addition, the findings of matrix effect, recovery, and stability were all within the acceptable limits. The new UPLC-MS/MS method was also successfully applied to characterize the pharmacokinetic changes of fedratinib in rats in the present of different antifungal drugs (such as isavuconazole, posaconazole, fluconazole and itraconazole). It turned out that fluconazole resulted in a prominent inhibitory effect on fedratinib metabolism in rats, followed by treatment with itraconazole and isavuconazole. Therefore, the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors may occur.

Objective To compare the effect of two internal fixation methods of calcaneal plate fixation and Philos plate fixation for the treatment of split fractures of the greater tuberosity of the humerus. Methods A retrospective analysis was carried out on the data of 37 patients with isolated split fractures of the greater tuberosity of the humerus treated in our hospital from September 2016 to April 2021. There were 24 males and 13 females, with an average of 46.7 (25-67) years old. All patients had fresh split fractures with displacement of >5mm and without other injuries (such as Bankart injury, SLAP injury and Hill-sachs injury). Enrolled patients were divided into two groups according to different internal fixation methods. Patients in group A were treated with calcaneal anatomical locking plate (n=16), and those in group B were given Proximal Humeral Internal Locking System (PHILOS) (n=21). Further comparison was conducted on the interval from injury to operation, length of incision, operation time, bleeding volume, postoperative Constant-Murley shoulder joint function score and complications between the two groups. Results All the 37 cases had fracture healing during the follow-up period ranging from 10-23 months, with an average of 11.9 months. The average interval from injury to operation was 3.7 days (2-4 days) in group A and 4.1 days (3-6 days) in group B, with no significant difference. The average length of incision was 6.2cm (4.5cm-7.3cm) in group A and 9.1cm (8.2cm-10.7cm) in group B, with significant difference. The average operation time was 61 minutes (51-77 minutes) in group A and 65 minutes (57-79 minutes) in group B, with no significant difference. There was significant difference in the comparison of bleeding volume between group A and group B [47ml (35ml-63ml) vs. 103ml (79ml-125ml)]. During the 6-month follow-up, the average Constant-Murley score was 87.5 points (76-97 points) in group A and 80.3 points (71-91 points) in group B, with significant difference. In addition, shoulder impingement syndrome occurred in 2 cases in group B, but not in group A. Conclusion Calcaneal anatomical locking plate can achieve satisfactory results in the treatment of adult fractures of the greater tuberosity of the humerus, with the advantages of less surgical trauma and less bleeding. Findings in our study can provide a new choice for the surgical treatment of isolated fractures of the greater tuberosity of the humerus.