人参皂苷Rh2两种差向异构体的HPLC含量测定

目的:建立2种人参皂苷Rh2异构体的高效液相色谱测定方法.方法:采用Merck LichrospherRP-18e C18色谱柱(250 mm×4.6 mm,5μm),流动相为CH3CN-CH3OH(65:35),检测波长为203 nm,流速为1.0 mL·min-1.结果:Rh2线性范围为0.06～1.20 g·L-1,以峰面积(y)对浓度(x,g·L-1)求得线性方程,S构型线性方程为y=2260.9x-12.533,r=0.9999;R构型线性方程为y=2596.1x-7.9654,r=0.9999.结论:本方法简便、准确、可靠,可用于Rh2中的2种差向异构体化合物的鉴别和含量测定.     

谈2012年全国卷(理二)第22题的解答

题目(2012年全国卷(二)第22题):函数f(x)=x2-2x-3,定义数列{xn}如下:x1=2,xn+1是过两点P(4,5),Qn(xn,f(xn))的直线PQn与x轴交点的横坐标.(Ⅰ)证明:2≤xn相似文献   

片重检查数理统计三题

1　有一批中药片剂 ,批号为 990 32 8。随机抽出 2 0片 ,分别称重 ,见表 1。已知理论值为 380 mg/片 ,问样本的实际片重与理论值是否存在显著性差异 ?解　列表统计 ,求得 x=383mg,Sx=∑n=2 0i=1(xi- x) 2n- 1=6 .93mg由给定条件 n=2 0 ,u0 =380 m g,属小样本 ,用 t法检验。假设 H0 :x=u0 ,则t=x- u0Sxn=383- 3806 .932 0=1.936查表 α=0 .0 5 ,df=n- 1=19,t1 - 0 .0 5 2 =2 .0 93|t|相似文献   

薄层扫描法测定香菊胶囊中黄芪甲苷的含量

目的　用薄层扫描法测定香菊胶囊中黄芪甲苷的含量。方法　双波长线性扫描 ,λS=5 30 nm,λR=70 0 nm;狭缝宽度 :0 .4 mm× 5 .0 mm;灵敏度 :中 ;展开剂 :氯仿 -甲醇 -水 (1 3∶ 7∶ 2 )下层溶液。结果　黄芪甲苷标准曲线线性范围 0 .6～ 3.6 μg;回归方程 :Y=35 4.6 3X +2 1 .0 2 ,r =0 .9992 ;平均回收率97.6 8% (n =5 ) ,RSD =2 .1 0 %。结论　方法简便、准确、易行 ,可用于香菊胶囊的质量控制     

曲线拟合后再拟合探讨

曲线拟合后 ,有时效果不理想。如将第一次拟合所得的估计值看作自变量与原因变量再作一次相近曲线拟合 ,可起到提高效果的目的。例 1　见表 1资料[1 ] :表 1　某地钩虫治疗次数与复查阳性率资料次数 x 12 3 45 678阳性率 (% ) y 63 .93 6.0 17.110 .5 7.3 4.5 2 .81.7原资料 y1 5 5 .73 3 .62 0 .2 12 .2 7.44 .42 .71.6本方法 y2 61.93 6.72 1.412 .3 6.83 .41.40 .2　　原资料用指数曲线拟合得 :y1 =92 .392 9e- 0 .50 6 2 x ,相关指数 R21 =0 .9738。将 y1 与 y再作散点图似呈直线关系 ,用直线拟合得 :y2 =1.14 0 5 y1 - 1.…     

兔血浆中地非三唑(DL111-IT)高效液相色谱荧光检测方法

目的　建立兔血浆中DL111 IT的高效液相色谱荧光检测法。方法　血浆样品和内标格列本脲经氯仿提取后 ,选用DiamonsilODS C18柱 (15 0mm× 4 . 6mm ,5 μm) ,乙腈 - 0 . 0 2 5mol·L-1磷酸氢二铵缓冲溶液 (磷酸调pH 5 .0 ) (6 0 .4 0 ,V/V)为流动相 ,流速 1 0mL·min-1,荧光检测 (λex=2 5 0nm ,λem=332nm)。结果　DL111 IT在浓度 1 .0 0～ 2 0. 0 0ng·mL-1范围内呈良好线性 ,r=0. 9996 ,n =5。高 (2 0 . 0 0ng·mL-1)、中 (10 . 0 0ng·mL-1)、低 (1 .0 0ng·mL-1) 3个质控样本平均提取回收率分别为85 . 3%± 1 .3% ,84 .9%± 2 . 7% ,85 . 8%± 1 .8% ,方法回收率分别为 99 .5 %± 0 . 4 % ,10 2 . 1%± 1. 8% ,10 .1 3%± 2 .4 % ;日内(n =5 )和日间 (n =5 )RSD分别低于 3 .0 %和 7. 0 %。血浆样品检测限为 0 3ng·mL-1(S/N =3) ,定量限为 1ng·mL-1(S/N =10 ,RSD <7 .0 % )。结论　本法准确、灵敏、操作简便 ,为DL111 IT药代动力学研究提供了方法学基础。     

薄层扫描法测定复方止咳胶囊中齐墩果酸含量

薄层扫描法测定复方止咳胶囊中齐墩果酸的含量。选用硅胶 G薄层板 ,氯仿 -甲醇 -冰醋酸 ( 2 0∶ 1∶ 0 .2 )为展开剂 ,双波长锯齿扫描 (λS=5 30 nm,λR=70 0 nm) ,齐墩果酸在 1～ 5μg呈良好的线性关系 ,平均回收率为 98.6% ( n =4) ,RSD为 2 .1 3%     

双波长薄层扫描法测定冠心通脉灵片中葛根素的含量

采用双波长薄层扫描法测定了冠心通脉灵片中葛根素的含量。氯仿 -甲醇 -水 (5∶ 2∶ 0 .2 )为展开剂 ,葛根素 Rf=0 .48,锯齿反射扫描 ,λS=2 70 nm,λR= 370 nm,SX=3,平均回收率为 99.60 % ,RSD =1 .1 3%     

高效液相色谱法测定人血浆中利鲁唑的浓度

目的　建立测定人血浆中利鲁唑浓度的 HPL C法。 方法 　以美国迪马公司 Diamonsil〔 TM〕C1 8反相柱 ( 2 5 0 mm× 4.6mm,5μm)为色谱柱 ,流动相为甲醇 -0 .0 3 mol·L- 1磷酸二氢铵 ( 80∶ 2 0 ,V/V) ,流速为 0 .8m L·min- 1 ,检测波长 2 65 nm,以乙醚为提取剂。结果 　利鲁唑高 ( 80 0 ng·m L- 1 、中 ( 10 0 ng· m L- 1 )、低 ( 10 ng· m L- 1 ) 3个浓度的平均回收率分别为 98.3 6%、96.47%、95 .14 %,日内、日间差 RSD均低于 5 %( n=5 ) ;分析方法的定量测定下限为 5 ng·m L- 1。线性范围为 :5～ 10 0 0 ng·m L- 1 ,回归方程为 Y=2 14 .44 x-5 .89,r=0 .999( n=8)。结论 　该方法灵敏、准确、简单、快速 ,可用于临床血浓监测和药动学研究     

高效液相色谱法梯度洗脱测定三七中三七皂苷R1含量

目的 :以HPLC梯度洗脱测定三七中三七皂苷R1含量。方法 :采用SphericorbNH2 柱 ,流动相为CH3CN CH3OH H2 O ,梯度洗脱浓度 5 5∶30∶15→ 70∶2 0∶10 ,波长 2 10nm ,外标一点法测定。结果 :以峰面积计算 ,三七皂苷R1在 5～ 40 μg·ml-1呈线性相关 ,γ =0 .994,最低检测限为 0 .6 μg·ml-1(S/N =3)。平均回收率 10 2 .6 % ,RSD为 1.43 % .日内误差RSD =1.7% (n =5 ) ,日间误差RSD =3 .0 % (n =4)。结论 :本法专属性强 ,结果准确 ,操作简捷     

Reactive sulfur species: kinetics and mechanism of the hydrolysis of cysteine thiosulfinate ester

The kinetics and mechanisms of the hydrolysis of cysteine thiosulfinate ester (CyS(O)SCy ( x- ), x = 0-2) have been investigated by stopped-flow spectrophotometry between pH 6 and pH 14. The rate-limiting reaction of hydroxide is observed for pH < 13. More complicated kinetics are observed above pH 13, where the hydrolysis of CyS(O)SCy (2-) can be fast relative to subsequent reactions. The eventual products of hydrolysis are a 1:1 molar ratio of cystine (CySSCy) and cysteine sulfinic acid (CySO 2H) under all reaction conditions. The rate of hydrolysis is dependent upon the proton state of CyS(O)SCy ( x- ). Furthermore, cysteine thiosulfonate ester (CyS(O) 2SCy) was observed as an intermediate during the hydrolysis of CyS(O)SCy ( x- ) at lower pH. CyS(O) 2SCy eventually hydrolyzes to give stoichiometric amounts of CySSCy and CySO 2H. However, CySO 2H is observed under some conditions for which hydrolysis of CyS(O) 2SCy is relatively slow, thus suggesting multiple hydrolysis pathways for CyS(O)SCy ( x- ). The mechanism up to the rate-limiting step is proposed to be as follows: CyS(O)SCy (0) = H (+) + CyS(O)SCy (-), p K a3 = 7.32; CyS(O)SCy (-) = H (+) + CyS(O)SCy (2-), p K a4 = 7.92; CyS(O)SCy (0) + OH (-) --> products, P 0 k 0 = (5.0 +/- 0.01) x 10 (3) M (-1) s (-1); CyS(O)SCy (-) + OH (-) --> products, P 1 k 1 = 60 +/- 18 M (-1) s (-1); and CyS(O)SCy (2-) + OH (-) --> products, P 2 k 2 = 0.36 +/- 0.01 M (-1) s (-1), where P x is a constant (1 相似文献   

Comparative study on pharmacological effects of DM-phencynonate hydrochloride and its optical isomers

AIM: The 3-azabicyclo(3,3,1)nonanyl-9-alpha-yl-alpha-cyclopentyl-alpha-phenyl-alpha-glycolate (DM-phencynonate hydrochloride, DMCPG) is a demethylated metabolite of 3-methyl-3-azabicyclo(3,3,1)nonanyl-9-alpha-yl-alpha-cyclopentyl-alpha-phenyl-alpha-glycolate (phencynonate hydrochloride, CPG). (+/-)DMCPG had one chiral center and two enantiomers [R(-) and S(+)DMCPG]. Here we carried out a comparative study of the pharmacological profiles of these optical isomers. METHODS: Affinity and relative efficacy were tested using a radioligand-binding assay with muscarinic acetylcholine receptors from the rat cerebral cortex. Pharmacological activity was assessed in three individual experiments: (1) potentiating the effect of a sub-threshold hypnotic dose of sodium pentobarbital; (2) inhibiting oxotremorine-induced salivation; and (3) inhibiting the contractile response to carbachol. RESULTS: In the competitive binding assay, R(-)DMCPG (K(i)=763.75 nmol/L) was 4- and 2-fold more potent than (+/-)DMCPG (K(i)=3186 nmol/L) and S(+)DMCPG (K(i)=1699 nmol/L) in inhibiting the binding of [(3)H]QNB. The R(-) and S (+) configurations showed positive cooperation (n(H)>1) with the muscarinic receptor, whereas (+/-)DMCPG had a negative cooperation (n(H)<1) relationship with the muscarinic receptor in a radio-binding assay. Both the R(-) and S(+) configurations could potentiate the effect of sub-threshold hypnotic dose of sodium pentobarbital in a dose-dependent manner (the ED(50) values were 2.53 and 18.65 mg/kg, respectively), but (+/-)DMCPG did not display significant central depressant effects at doses from 10 to 29.15 mg/kg (P>0.05). (+/-)DMCPG and its optical isomers suppressed the guinea pig ileum contractile response to carbachol. The IC(50) values were 7.78 x 10(-9), 1.88 x 10(-7), and 1.038 x 10(-7) nmol/L, respectively. In the anti-salivation study, (+/-)DMCPG and its enantiomers depressed oxotremorine- induced salivation in a dose-dependent manner, and the order of potency was R(-)DMCPG (ED(50)=0.44 mg/kg) > (+/-)DMCPG (ED(50)=2.88 mg/kg) >S(+)DMCPG (ED(50)=5.05 mg/kg). CONCLUSION: (+/-)DMCPG and its optical isomers have differences in their pharmacological potencies as anticholinergic agents, and the R(-) configuration is more active than the S(+) configuration.     

Effect of the ecto-ATPase inhibitor, ARL 67156, on the bovine chromaffin cell response to ATP

Bovine chromaffin cells contain an ecto-ATPase (K(m)=1.57 +/- 0.27 x 10(-4) M) which can hydrolyze ATP present in the culture media. ARL 67156 is a competitive inhibitor of this ATPase (K(i)=2.55 +/- 1.36 x 10(-7) M). A small increase in potency (threefold) is seen when ARL 67156 is included during measurement of ATP-stimulated inositol phosphate formation. ARL 67156 also acts on chromaffin cell P2Y receptors to increase inositol phosphate formation (EC(50)=4.9 x 10(-5) M). It is useful as an ecto-ATPase inhibitor in studies with bovine chromaffin cells since it exhibits a 300-fold selectivity for the ecto-ATPase versus the P2Y receptor.     

Clinical usefulness of limited sampling strategies for estimating AUC of proton pump inhibitors

Cytochrome P450 (CYP) 2C19 (CYP2C19) genotype is regarded as a useful tool to predict area under the blood concentration-time curve (AUC) of proton pump inhibitors (PPIs). In our results, however, CYP2C19 genotypes had no influence on AUC of all PPIs during fluvoxamine treatment. These findings suggest that CYP2C19 genotyping is not always a good indicator for estimating AUC of PPIs. Limited sampling strategies (LSS) were developed to estimate AUC simply and accurately. It is important to minimize the number of blood samples because of patient's acceptance. This article reviewed the usefulness of LSS for estimating AUC of three PPIs (omeprazole: OPZ, lansoprazole: LPZ and rabeprazole: RPZ). The best prediction formulas in each PPI were AUC(OPZ)=9.24 x C(6h)+2638.03, AUC(LPZ)=12.32 x C(6h)+3276.09 and AUC(RPZ)=1.39 x C(3h)+7.17 x C(6h)+344.14, respectively. In order to optimize the sampling strategy of LPZ, we tried to establish LSS for LPZ using a time point within 3 hours through the property of pharmacokinetics of its enantiomers. The best prediction formula using the fewest sampling points (one point) was AUC(racemic LPZ)=6.5 x C(3h) of (R)-LPZ+13.7 x C(3h) of (S)-LPZ-9917.3 x G1-14387.2×G2+7103.6 (G1: homozygous extensive metabolizer is 1 and the other genotypes are 0; G2: heterozygous extensive metabolizer is 1 and the other genotypes are 0). Those strategies, plasma concentration monitoring at one or two time-points, might be more suitable for AUC estimation than reference to CYP2C19 genotypes, particularly in the case of coadministration of CYP mediators.     

Dualistic actions of cromakalim and new potent 2H-1,4-benzoxazine derivatives on the native skeletal muscle K ATP channel

1 New 2H-1,4-benzoxazine derivatives were synthesized and tested for their agonist properties on the ATP-sensitive K(+) channels (K(ATP)) of native rat skeletal muscle fibres by using the patch-clamp technique. The novel modifications involved the introduction at position 2 of the benzoxazine ring of alkyl substituents such as methyl (-CH(3)), ethyl (-C(2)H(5)) or propyl (-C(3)H(7)) groups, while maintaining pharmacophore groups critical for conferring agonist properties. 2 The effects of these molecules were compared with those of cromakalim in the presence or absence of internal ATP (10(-4) M). In the presence of internal ATP, all the compounds increased the macropatch K(ATP) currents. The order of potency of the molecules as agonists was -C(3)H(7) (DE(50)=1.63 x 10(-8) M) >-C(2)H(5) (DE(50)=1.11 x 10(-7) M)>-CH(3) (DE(50)=2.81 x 10(-7) M)>cromak-slim (DE(50)= 1.42 x 10(-5) M). Bell-shaped dose-response curves were observed for these compounds and cromakalim indicating a downturn in response when a certain dose was exceeded. 3 In contrast, in the absence of internal ATP, all molecules including cromakalim inhibited the K(ATP) currents. The order of increasing potency as antagonists was cromakalim (IC(50)=1.15 x 10(-8) M)> or =-CH(3) (IC(50)=2.6 x 10(-8) M)>-C(2)H(5) (IC(50)=4.4 x 10(-8) M)>-C(3)H(7) (IC(50)=1.68 x 10(-7) M) derivatives. 4 These results suggest that the newly synthesized molecules and cromakalim act on muscle K(ATP) channel by binding on two receptor sites that have opposite actions. Alternatively, a more simple explanation is to consider the existence of a single site for potassium channel openers regulated by ATP which favours the transduction of the channel opening. The alkyl chains at position 2 of the 2H-1,4-benzoxazine nucleus is pivotal in determining the potency of benzoxazine derivatives as agonists or antagonists.     

Pharmacological characterisation of cannabinoid receptors inhibiting interleukin 2 release from human peripheral blood mononuclear cells

The effects of a range of cannabinoid receptor agonists and antagonists on phytohaemagglutinin-induced secretion of interleukin-2 from human peripheral blood mononuclear cells were investigated. The nonselective cannabinoid receptor agonist WIN55212-2 ((R)-(+)-[2,3-dihydro-5-methyl-3-[4-morpholinylmethyl]pyrrolo[1,2,3-de]1,4-benzoxazin-6-yl](1-naphthyl) methanone mesylate) and the selective cannabinoid CB(2) receptor agonist JWH 015 ((2-methyl-1-propyl-1H-indol-3-yl)-1-napthalenylmethanone) inhibited phytohaemagglutinin (10 microg/ml)-induced release of interleukin-2 in a concentration-dependent manner (IC(1/2max), WIN55212-2=8.8 x 10(-7) M, 95% confidence limits (C.L.)=2.2 x 10(-7)-3.5 x 10(-6) M; JWH 015=1.8 x 10(-6) M, 95% C.L.=1.2 x 10(-6)-2.9 x 10(-6) M, n=5). The nonselective cannabinoid receptor agonists CP55,940 ((-)-3-[2-hydroxy-4-(1,1-dimethyl-hepthyl)-phenyl]4-[3-hydroxypropyl]cyclo-hexan-1-ol), Delta(9)-tetrahydrocannabinol and the selective cannabinoid CB(1) receptor agonist ACEA (arachidonoyl-2-chloroethylamide) had no significant (P>0.05) inhibitory effect on phytohaemagglutinin-induced release of interleukin-2. Dexamethasone significantly (P<0.05) inhibited phytohaemagglutinin-induced release of interleukin-2 in a concentration-dependent manner (IC(1/2max)=1.3 x 10(-8) M, 95% C.L.=1.4 x 10(-9)-3.2 x 10(-8) M). The cannabinoid CB(1) receptor antagonist SR141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride) (10(-6) M) did not antagonise the inhibitory effect of WIN55212-2 whereas the cannabinoid CB(2) receptor antagonist SR144528 (N-(1,S)-endo-1,3,3-trimethyl bicyclo(2,2,1)heptan-2-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide) antagonised the inhibitory effect of WIN55212-2 (pA(2)=6.3+/-0.1, n=5). In addition, CP55,940 (10(-6) M) and Delta(9)-tetrahydrocannabinol (10(-6) M) also antagonised the inhibitory effects of WIN55212-2 (pA(2)=6.1+/-0.1, n=5 and pA(2)=6.9+/-0.2, n=5). In summary, WIN55,212-2 and JWH 015 inhibited interleukin-2 release from human peripheral blood mononuclear cells via the cannabinoid CB(2) receptor. In contrast, CP55,940 and Delta(9)-tetrahydrocannabinol behaved as partial agonists/antagonists in these cells.     

On iontophoretic delivery enhancement: ionization and transport properties of lidocaine hydrochloride in aqueous propylene glycol

The ionization and transport properties of lidocaine hydrochloride (LidHCl) in aqueous propylene glycol (PG) containing 20% PG by weight was studied by means of electrical precision conductometry. For drug concentrations exceeding about 1.7 mM a slight formation of LidH(+)Cl(-) ion-pairs is indicated; ion-pair association constant, K(p)=1.73 (molar scale). A two variable analysis of the experimental data yielded K(a)=1.5x10(-8) for the acid dissociation constant of LidH(+), i.e. pK(a)=7.82, and the limiting ionic conductivity, lambda(o)(LidH(+))=21.73 cm(2) S mol(-1). To enable evaluation of single ion conductivities the proton transport number of HCl in the present solvent mixture was determined using the moving boundary method.     

Synthesis and anticonvulsant activity of novel 1-substituted-1,2-dihydro-pyridazine-3,6-diones

The synthesis and pharmacological evaluation of novel 1-substituted-1,2-dihydro-pyridazine-3,6-diones (4a--l, 5a--j) as potential anticonvulsant agents are described. The compounds were tested in vivo for the anticonvulsant activity. The compound which have maximum protection against MES induced seizures is 1-[3-(2-aminophenylamino)-2-hydroxypropyl)-1,2-dihydro-pyridazine-3,6-dione 4h (ED(50)=44.7 mg x kg(-1) i.p.) 1-[2-hydroxy-3-piperazin1-yl-propyl)-1,2-dihydro-pyridazine-3,6-dione 4c (ED(50)=72 mg x kg(-1) i.p.) and 1-[2-hydroxy-3-imidazol-1-yl-propyl)-1,2-dihydro-pyridazine-3,6-dione 4d (ED(50)=79 mg x kg(-1) i.p.) were also found to have maximum protection against MES induced seizures. Whereas all these compounds failed to protect the animals from subcutaneous pentylenetetrazole (Metrozol) seizure threshold test (sc-Met).     

Comparative in vitro bacteriostatic and bactericidal activity of trovafloxacin, levofloxacin and moxifloxacin against clinical and environmental isolates of Legionella spp.

The susceptibility of 140 Legionella spp isolates (106 clinical and 34 environmental isolates) to trovafloxacin (TRFX), levofloxacin (LEVX), moxifloxacin (MOFX), ciprofloxacin (CIPX), ofloxacin (OFLX), erythromycin (ERY), azithromycin (AZI) and rifampicin (RIF) was studied using a standard microdilution method and buffered yeast extract broth (BYE) supplemented with 0.1% alpha-ketoglutarate. The post-antibiotic effects (PAEs) of the study drugs against 10 clinical isolates of Legionella pneumophila sg.1 were compared. The MIC inhibiting 90% of strains tested on BYEalpha broth were 0.008, 0.016, 0.016, 0.06, 0.125, 0.5, 0.5, and 0.004 mg/l for TRFX, LEVX, MOXX, CIP, OFLX, ERY, AZI, and RIF, respectively. The MBC/MIC ratios ranged from one to eight depending on the antibiotic tested: TRFX [1x-2 x MIC], LEVX, MOFX, CIPX and OFLX [1x-4 x MIC], RIF [2x-4 x MIC], ERY and AZI [2x-8 x MIC]. TRFX, RIF, LEVX, MOFX, CIPX, OFLX, ERY and AZI showed similar activity against Legionella species other than L. pneumophila. One-hour exposures to the study antimicrobial agents at a concentration of 4 x MIC resulted in PAEs as follows (average in hours): TRFX: 2.68 h; RIF: 2.63 h; CIPX: 2.62 h; MOFX: 2.56 h; LEVX: 2.41 h; OFLX: 2.25 h; AZI: 1.65 h; and ERY: 1.54 h. In conclusion, our in vitro data confirm that trovafloxacin, levofloxacin, moxifloxacin and rifampicin have excellent bacteriostatic and bactericidal activity against Legionella spp and show significant post-antibiotic effect.     

In vitro evaluation of alkylcarbonyloxymethyl (ACOM) ethers as novel prodrugs of phenols for topical delivery: ACOM prodrugs of acetaminophen

The fluxes (J(IPM)) of a series of alkylcarbonyloxymethyl (ACOM) ethers of acetaminophen (APAP) were measured through hairless mouse skin from suspensions of each prodrug in isopropyl myristate (IPM). Solubilities in IPM, estimated solubilities in pH 4.0 buffer (S(4.0)) and flux data for the 4-ACOM-APAP prodrugs were incorporated into the Roberts-Sloan (RS) database to give new estimates for the independent variables of the RS equation: logJ(IPM)=x+ylogS(IPM)+(1-y)logS(4.0)-zM(W). All but one of the 4-ACOM-APAP derivatives hydrolyzed completely on permeation through mouse skin. Three out of the five prodrugs permeated the skin better than APAP, with a maximum fourfold increase in flux. Biphasic solubility - not solubility in a single solvent - was shown to have the greatest impact on flux. A fit of the new n=66 database to the RS equation gave the following values for x, y, z, and r(2): x=-0.545, y=0.511, z=0.00253, r(2)=0.915. These results demonstrate that the topical delivery of a model phenol, acetaminophen, can be improved by transiently masking the phenolic hydroxyl group as an ACOM ether.