液质联用同时测定大鼠尿液中6种苯二氮卓类药物

建立高效液相色谱串联质谱法同时测定大鼠尿液中的6种苯二氮卓类药物（BZDs）。以乙酸乙酯为萃取溶剂，经液-液萃取前处理后检测。以地西泮为内标，流动相为甲醇-0.01%甲酸+5 mmol／L甲酸铵，梯度洗脱，柱温为40℃；流速为0.3 mL／min；进样量为2 μL，质谱采用电喷雾离子源正离子模式（ESI⁺）。8-溴-1-甲基-6-吡啶-2-基-4H-［1，2，4］三唑并［4，3-a］-1，4苯并二氮杂卓（Pyrazolam）、氯硝西泮（5-［2-氯苯基］-l，3-二氢-7-硝基-2H-1，4-苯二氮卓-2-酮，Clonazepam）、8-溴-6-［2-氟苯基］-1-甲基-4H-［1，2，4］三唑［4，3a］［1，4］苯并二氮杂卓（Flubromazolam）、甲氯西泮（（S）-5-［2-氯苯基］-1，3-二氢-3-甲基-7-硝基-2H-1，4-苯并二氮杂卓-2-酮，Meclonazepam）、7-溴-5-［2-氟苯基］-1，3-二氢-2H-1，4-苯并二氮杂-2-酮（Flubromazepam）和2′-氯地西泮（7-氯-5-［2-氯苯基］-1，3-二氢-1-甲基-2H-1，4-苯并二氮杂卓-2-酮，Diclazepam）共6种BZDs在20～2000 ng／mL范围内均有良好的线性，日内和日间精密度均在0.70%～5.60%之间，准确度均在87.00%～103.00%，提取回收率基本均>80.00%，稳定性良好。该方法快速、简便、灵敏和准确，适用于大鼠尿液中6种BZDs的同时测定。

Simultaneous Determination of Six Benzodiazepines in Rat Urine by Liquid Chromatography Tandem Mass Spectrometry

A liquid chromatography tandem mass spectrometry method is established for the simultaneous determination of six benzodiazepines(BZDs)in rat urine.Ethyl acetate is used as the extraction solvent,and it is tested after liquid-liquid extraction pretreatment.Diazepam is used as the internal standard,the mobile phase is methanol-(0.01% formic acid+5 mmol/L ammonium formate)with a gradient elution,the column temperature is 40℃;the flow rate is 0.3 mL/min and the injection volume is 2μL.The electrospray ion source is in positive ion mode(ESI+).The six BZDs(pyrazolam:8-bromo-1-methyl-6-pyridin-2-yl-4H-1,2,4]triazolo4,3-a]1,4]benzodiazepine;clonazepam:5-2-chlorophenyl]-l,3 dihydro-7-nitro-2H-benzodiazepin-2-one;flubromazolam:8-bromo-6-2-fluorophenyl]-1-methyl-4H-1,2,4]triazolo-4,3 a]1,4]benzodiazepine;meclonazepam:3(+)-5-(o-chlorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazpine-2-one;flubromazepam:7-bromo-5-2-fluorophenyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one;diclazepam:7-chloro-5-2-chlorophenyl]-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one)all have good linearity in the range of 20~2000 ng/mL,and the intraday and interday precisions of both 0.70%~5.60%.In the meantime,the accuracy is between 87.00% and 103.00%,and extraction recoveries of six analytes are greater than 80.00%,and the stability is good.The method is fast,simple,sensitive and accurate,which is suitable for the simultaneous measurement of the concentrations of six BZDs in rat urine.