Objective To establish a rapid and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis method for determination of unsymmetrical dimethylhydrazine(UDMH)contents in rat plasma and investigate the toxicokinetic characteristics of UDMH in rats.Methods Twenty-two SD rats were divided into the intravenous injection of 10 mg/kg dose group(4 females)and intragastric administration groups(low,medium and high dose,with 6 rats in each group,half males and half females).The rats were given 10mg/kg by intravenous administration and 10 mg/kg,30 mg/kg,and 90 mg/kg single dose of UDMH by gavage.Blood samples were collected from the orbital venous plexus at 0 hour before administration and at different time points after administration.The plasma samples were extracted with protein precipitation and derivatization before being analyzed using the LC-MS/MS method.Separation was carried out on a ZORBAX column(4.6mm×75mm,3.5 μm),with a mobile phase composed of 0.3％acetonitrile/formic acid at a flow rate of 1 mL/min.Propranolol was used as the internal standard.An electrospray ionization(Turbo Ionspray)source was applied and the mass spectrometer was operated in a positive MRM mode.Quantitative analysis showed that the ionization source unsymmetrical dimethylhydrazine and propranolol was at m/z:192.0→148.1,m/z:260.2→116.1,respectively.The toxicokinetic parameters were analyzed with the DAS 2.1 software.Results Quantification of UDMH exhibited a good linearity within the concentration range of 50-50000 ng/mL,with a linear correlation coefficient greater than 0.9900 and a lower limit of quantification of 50 ng/mL.The average recovery rate of UDMH was 98.1％,compared with 100.5％for the internal standard propranolol hydrochloride.The inter batch precision of standard curve samples ranged from 0.7％to 6.3％,and the relative error was between-7.1％and 6.2％.The inter batch and intra batch precision of quality control samples ranged from1.8％to 19.8％,and the relative error from-9.8％to 0.2％.The main pharmacokinetic parameters of UDMH in rats exposed to 10 mg/kg,30 mg/kg,and 90 mg/kg gavage were UC(0-t):(7624.99±2569.31),(34284.04±6657.15),(84720.88±22354.80)μg/L·h,t1/2:(0.07±0.15),(2.24±1.45),(3.04±0.90)h,Tmax:(0.75±0.27),(0.51±0.29),(0.29±0.10)h,Cmax:(4454.14±1329.45),(19442.45±9121.07),(32334.35±9882.41)μg/L,F:(77.34±26.06)％,(115.92±22.51)％,(95.48±25.19)％.Conclusion The LC-MS/MS method is highly accurate and specific,and is suitable for the toxicokinetic study of UDMH in rats.Single gavage administration of UDMH results in absorption and elimination saturation at a high dose.This study provides data for toxicological studies related to UDMH.

[Abstrca t] Objective BRCA 1 ( breast cancer susceptibility gene 1) and RAP80 ( receptor-associated protein 80) play key roles in predicting chemosensitivity of platinum and taxanes .A randomized trial was carried out to compare non-selected cisplatin-based chemotherapy with therapy customized according to BRCA1 and RAP80 expression.Methods Advanced stage NSCLC patients whose tumor specimen was sufficient for molecular analysis were randomized (1∶3) to the control or experimental arm.Patients in the control arm received docetaxel/cisplatin; in the experimental arm , patients with low RAP 80 expression received gemcitabine/cisplatin ( Arm 1 ) , those with intermediate/high RAP 80 expression and low/intermediate BRCA 1expression received docetaxel/cisplatin ( Arm 2 ) , and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone (Arm 3).The primary end point was progression-free survival (PFS).Results 226 patients were screened and 124 were randomized in this trial.ORR in the four subgroups was 22.6%, 48.4%, 30.3%and 19.2%, respectively (P=0.08);PFS was 4.74, 5.59, 3.78 and 2.73 months, respectively (P=0.55); and OS was 10.82, 14.44, 10.86 and 10.86 months, respectively (P=0.84).The common adverse effects included neutropenia , nausea, anemia and fatigue.Conclusions No statistically significant difference of ORR , PFS or OS is observed in the experimental arms compared with the control arm .Patients with low RAP 80 mRNA levels have a trend of better survival and higher response rate to gemcitabine /cisplatin chemotherapy .

[Abstrca t] Objective BRCA 1 ( breast cancer susceptibility gene 1) and RAP80 ( receptor-associated protein 80) play key roles in predicting chemosensitivity of platinum and taxanes .A randomized trial was carried out to compare non-selected cisplatin-based chemotherapy with therapy customized according to BRCA1 and RAP80 expression.Methods Advanced stage NSCLC patients whose tumor specimen was sufficient for molecular analysis were randomized (1∶3) to the control or experimental arm.Patients in the control arm received docetaxel/cisplatin; in the experimental arm , patients with low RAP 80 expression received gemcitabine/cisplatin ( Arm 1 ) , those with intermediate/high RAP 80 expression and low/intermediate BRCA 1expression received docetaxel/cisplatin ( Arm 2 ) , and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone (Arm 3).The primary end point was progression-free survival (PFS).Results 226 patients were screened and 124 were randomized in this trial.ORR in the four subgroups was 22.6%, 48.4%, 30.3%and 19.2%, respectively (P=0.08);PFS was 4.74, 5.59, 3.78 and 2.73 months, respectively (P=0.55); and OS was 10.82, 14.44, 10.86 and 10.86 months, respectively (P=0.84).The common adverse effects included neutropenia , nausea, anemia and fatigue.Conclusions No statistically significant difference of ORR , PFS or OS is observed in the experimental arms compared with the control arm .Patients with low RAP 80 mRNA levels have a trend of better survival and higher response rate to gemcitabine /cisplatin chemotherapy .