An accurate and validated liquid chromatography method and a triple quadrupole mass spectrometry method were developed and validated to simultaneously evaluate the cytochrome P450 (CYP) enzymes in vivo using the co-administration of these probes. @entity8169 , @entity9886 , @entity1406 and @entity1363 were used as the probe substrates for @entity35 @entity7771 , @entity11042 , @entity22934 and @entity7570 enzymes, respectively. The purpose of the study was to investigate the effect of @entity17170 on these cytochrome P450 enzymes in vivo with co-administration of these probes. Plasma samples were prepared by precipitating protein with @entity1626 . The analytes were separated using a reversed-phase BEH C18 column (2.1mm*100mm, 1.7 m, Waters, USA) maintained at 40  C. The mobile phase consisted of @entity1626 and water (containing 0.1% @entity5189 ) with a gradient elution pumped at a flow rate of 0.4mL/min. The analytes were detected with positive electrospray ionization in multiple reaction monitoring (MRM) mode for target fragment ions m/z 180.05 > 109.94 for @entity8169 , m/z 423.1 > 207.2 for @entity9886 , m/z 268.12 > 115.8 for @entity1406 , m/z 326.02 > 290.99 for @entity1363 and m/z 285.1 > 193.1 for @entity3175 (IS). Good linearity was achieved to quantify the concentration ranges of 10-2000ng/mL for @entity8169 , 10-1000ng/mL for @entity9886 , 10-1000ng/mL for @entity1406 and 1-100ng/mL for @entity1363 in @entity35 plasma. The mean recoveries of @entity8169 , @entity9886 , @entity1363 and @entity1406 from the plasma exceeded 77.07%. The intra-run and inter-run assay precisions were both less than 8.9%. This method was successfully applied to evaluate the effects of @entity17170 on the cytochrome P450 enzymes in @entity35 .

Evaluation of the effect of @entity17170 (YN968D1) on cytochrome P450 enzymes with cocktail probe drugs in XXXX by UPLC-MS/MS.

@entity3175 :: ('MESH:D003975', 'Chemical') :: ['diazepam'] @entity1626 :: ('MESH:C032159', 'Chemical') :: ['acetonitrile'] @entity22934 :: ('171522(Tax:10116)', 'Gene') :: ['CYP2D4'] @entity11042 :: ('29277(Tax:10116)', 'Gene') :: ['CYP2C11'] @entity9886 :: ('MESH:D019808', 'Chemical') :: ['losartan'] @entity7570 :: ('25642(Tax:10116)', 'Gene') :: ['CYP3A1'] @entity1406 :: ('MESH:D008790', 'Chemical') :: ['metoprolol'] @entity17170 :: ('MESH:C553458', 'Chemical') :: ['apatinib'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity7771 :: ('24297(Tax:10116)', 'Gene') :: ['CYP1A2'] @entity8169 :: ('MESH:D010615', 'Chemical') :: ['phenacetin', 'Phenacetin'] @entity1363 :: ('MESH:D008874', 'Chemical') :: ['midazolam'] @entity5189 :: ('MESH:C030544', 'Chemical') :: ['formic acid']
@entity35 :: (10116,Species) :: ['rats']
