ABSTRACT
OBJECTIVE To provide theoretical basis for the rational use of drugs in medical institutions， assist in improving the quality of pharmaceutical services， and thus meet clinical drug demands. METHODS Adopting consensus meetings， Liaoning Pharmaceutical Association，Jilin Pharmaceutical Association and Heilongjiang Pharmaceutical Association collaborated with clinical and pharmaceutical experts in the region to compile the expert consensus on off-label drug use in the three Northeastern provinces of China after many votes and discussions by collecting and collating the information related to off-label drug use in medical institutions from the three northeastern provinces of China，and referring to and citing off-label drug use stated in some expert consensus and medication catalog. RESULTS Finally， a total of 198 pieces of off-label drug use information for 70 drugs were included in the two sections of solid tumors and hematological diseases in Consensus of Experts on Drug Use beyond the Instructions in the Three Provinces of Northeast China. CONCLUSIONS Consensus of Experts on Off-label Drug Use in the Three Northeastern Provinces of Northeast China （solid tumors and hematology）offers a theoretical foundation for rational drug use in the treatment of solid tumors and hematological diseases within medical institutions，and has a positive significance in improving the effectiveness and safety of drug treatment.
ABSTRACT
OBJECTIVE：To establish the method for simultaneous determination of 5-fluorouracil（5-FU）and its metabolites 5-fluoro-5，6-dihydrouracil （5-FUH2） in human plasma ，and apply it in the clinic. METHODS ：After plasma samples were processed twice by ethyl acetate ，UPLC-MS/MS method was adopted using 5-bromouracil （5-Bru） as internal standard. The determination was performed on Acquity UPLC HSS T 3 column with mobile phase consisted of methanol-water （30 ∶ 70，V/V）at the flow rate of 0.3 mL/min. The column temperature was 20 ℃，and sample size was 5 μL. An electrospray ion source was used to carry out negative ion scanning with multiple reaction monitoring. The capillary voltage was 1.5 kV；the taper hole voltage was 20 V；the desolvent temperature was 450 ℃；the desolvent air flow was 850 L/h；the cone hole gas velocity was 50 L/h. The ion transitions for quantitative analysis were m/z 129.00→41.90（5-FU），m/z 130.87→82.92（5-FUH2），m/z 189.00→42.10（5-Bru）， respectively. From Aug. to Oct. 2020，10 patients with advanced colorectal cancer were treated with continuous intravenous drip of 5-FU for 46 hours were collected from Harbin Medicinal University Cancer Hospital. Steady-state plasma concentration of 5-FU and plasma concentration of 5-FUH2 were determined at 18-30 h of continuous intravenous drip. The area under the curve （AUC）for 5-FU and concentration ratio of 5-FUH2/5-FU were calculated. RESULTS ：The linear range of 5-FU and 5-FUH2 were 20 to 1 000 μg/mL（R 2＞0.990）. The quantification limits were 20 ng/mL. RSDs of precision test were all lower than 20％，and relative error ranged ±10％. The extraction recovery and matrix effects didn ’t affect the determination of substance to be measured. Among 10 patients with advanced colorectal cancer ，the steady-state concentration of 5-FU were 180.04-622.83 ng/mL，and AUC of 5-FU ranged from 8.28 to 28.65 mg·h/L. The concentration of 5-FUH2 ranged 336.48-948.43 ng/mL，and concentration ratio of 5-FUH2/ 5-FU ranged 0.93-4.21. AUC of 5-FU in 10 patients had about 3-4 fold individual differences. CONCLUSIONS ：The established method has good precision and accuracy ，high sensitivity ，and simple operation. It can be used for plasma monitoring of 5-FU in patients with advanced colorectal cancer.