The integrated analysis strategy of unstable hypoxanthine, a potential quality marker in Shuxuetong injection based on standard addition method and multi-level pharmacokinetics by LC-MS/MS

Abstract

Objective: As an injection made from traditional Chinese medicine, Shuxuetong (SXT) injection is used for the treatment of ischemic stroke. Hypoxanthine is regarded as one of its potential quality markers. The purpose of this study is to lay the foundation for the quality control of SXT injection by the analysis of the quantitation and pharmacokinetic behavior of hypoxanthine. Methods: A quantitative method of hypoxanthine in SXT injection based on standard addition method by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established for the first time. On the other hand, a determination method of hypoxanthine in rat plasma samples after administration of SXT was also successfully established based on LC-MS/MS. Results: It was found that the content of hypoxanthine was higher using conventional liquid-mass spectrometry technology compared to the application of LC-MS/MS combined standard addition method in the same batch of SXT injection. The ratio of low, medium and high doses of intravenous SXT were 1:2:4, and the AUC0-t was (848.34 ± 324.53) μg·h/L, (1483.94 ± 497.74) μg·h/L, and (3074.84 ± 910.29) μg·h/L, respectively. AUC0-t shows a good linear dose-dependent relationship. Conclusions: The influences of endogenous substances tend to be eliminated by calibrating the concentration level of the target compound by the introduction of the standard addition method. The added allopurinol could inhibit the conversion of the target compound, and ensure the accuracy of the detection during the pharmacokinetic studies. “Blank biological matrix” obtained from the pretreatment of blank plasma successfully distinguished endogenous and drug-derived hypoxanthine. There is a good linear relationship between the blood concentration of intravenous hypoxanthine and the dosage of administration. Similarly, there was no drug accumulation in the multiple medium-dosage group, which is similar to the pharmacokinetic characteristics of the single medium-dosage group. Graphical abstract: http://links.lww.com/AHM/A59

Association between stroke and venous leg ulcers: A Mendelian randomization study

“…Stroke is a common neurological disorder and survivors often have multiple sequelae. 10,11 Patients admitted to the hospital for stroke are at risk for deep vein thrombosis (DVT), 12 which plays a critical role in VLUs. 13 Therefore, this raises doubts about a possible causal relationship between these two diseases.…”

“…Treatment outcomes may be enhanced by a deeper comprehension of the elements that lead to nonhealing VLUs. Stroke is a common neurological disorder and survivors often have multiple sequelae 10,11 . Patients admitted to the hospital for stroke are at risk for deep vein thrombosis (DVT), 12 which plays a critical role in VLUs 13 .…”

Quantification and discovery of quality markers from Toddalia asiatica by UHPLC‐MS/MS coupled with chemometrics

“…[7][8][9][10][11][12] Ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) is a potent analytical technique known for its prominent performance in chromatograph separation and signal acquisition. 13 Multiple reaction monitoring (MRM), a robust data acquisition mode featuring high selectivity, high resolution, and high sensitivity, is primarily performed in triple quadrupole mass spectrometry or hybrid triple quadrupole linear ion trap MS, which can effectively eliminate interference from co-eluting components in the analysis program. [14][15][16] Given the complicated and versatile chemical composition of TA, it is a practicable task to refine its quality evaluation system using UHPLC-MS/MS.…”