Establishment Of Venetoclax Analysis Based On HPLC-MS/MS And Its Application In Individualized Treatment Of Acute Myeloid Leukemia

Acute myeloid leukemia(AML)is a kind of hematological disease caused by malignant clones of myeloid Hematopoietic stem cell.It can inhibit the hematopoietic function of patients.The main clinical manifestations of AML are infection,anemia and fever,liver,spleen and lymphadenopathy may be present in some severe cases.The disease progresses rapidly,is difficult to control,seriously endangers the patient's life-level quality of life.The cause of acute myeloid leukemia has not been determined exactly until now.It may be related to both genetic and biological factors,viral infection,radiation damage,chemical toxicity and drug toxicity may all lead to AML.At present,the methods of cell morphology,immunology,cytogenetics and molecular biology are mainly used in clinical diagnosis.Currently,the treatment of AML is based on induction chemotherapy with Anthracycline and Nucleoside analogue followed by consolidation therapy with high-dose cytarabine regimens or blood stem cell transplantation.Venetoclax is a selective inhibitor of B-cell lymphoma-2(BCL-2),f DA-APPROVED anti-tumor therapy for patients with leukemia,lymphocyte lymphoma and acute myeloid leukemia.The results showed that Venetoclax alone was well tolerated,but the efficacy was limited and there were some side effects.The study found that combination therapy appears to improve outcomes compared with Venetoclax monotherapy to overcome the shortcomings of monotherapy in the clinic.LC-MS-MS-RRB-method for simultaneous determination Venetoxetox,cytarabine and Voriconazole in human plasma,and to explore the relationship between serum concentration and clinical efficacy,adverse drug reactions,dosage and combination of Venetoclax.OBJECTIVEThere is a strong correlation between the plasma concentration of venetoclax and its clinical efficacy,adverse reactions and combination therapy.In order to improve the therapeutic effect of drugs and reduce the incidence of adverse drug reactions,it is very important to establish the TDM method with venetoclax.In this study,a High-performance liquid chromatography-mass spectrometry(LC-MS-MS-RRBmethod was developed for the simultaneous determination Venetoxetox,cytarabine and Voriconazole in human plasma.In addition,the aim of this study was to explore the relationship between venetoclax plasma concentration and clinical efficacy and adverse drug reactions after detection of venetoclax plasma concentration by this method.METHODSThe plasma samples were pretreated with methanol as precipitator and the column was a Kinetex C18 liquid chromatography column(2.1 × 50 mm,2.6 μm),and the column temperature was 40 ° C Esi ion source was used to detect the sample.The patients who were normally taking venetoclax,cytarabine and Voriconazole from May2022 to March 2022 in a third-grade a hospital were selected,the plasma samples were collected after one week of continuous administration and the drug concentration was determined by LC-MS/MS.The clinical efficacy was evaluated by RECIST,and the patients were divided into complete response(CR),partial response(PR),stable disease(SD-RRB-and progression of disea PD(PD).Adverse events were assessed as thrombocytopenia,cough,and myelosuppression.SPSS23.0 software was used to analyze the data.RESULTSThe single-needle analysis time of chromatographic separation and mass spectrometry was 5 min,and the specificity was good.The linear relationship of the compounds to be determined was good in the range of 2 ~ 5000,2 ~ 2000,5 ~ 2000ng/ml,Cytarabine and Voriconazole,the correlation coefficients were all greater than0.995.In accordance with the“Chinese pharmacopoeia” requirements,methodological review of each of these are in line with the requirements.There was no significant correlation between venetoclax serum concentration and sex,age,clinical efficacy,and adverse drug reaction(ADR).There was no significant correlation between the plasma concentration of venetoclax and the dose of Voriconazole,but there was no significant correlation between the plasma concentration of venetoclax and the dose of cytarabineCONCLUSIONSThe LC-MS-MS method developed in this study has high specificity and sensitivity,and can be used for the clinical determination of venetoclax,Cytarabine and Voriconazole.The cough side effects were more likely to occur at higher concentrations of venetoclax,and when venetoclax was used with Voriconazole,the level of venetoclax in patients blood increased significantly.