酒石酸酯/β-环糊精分离体系分离α-环己基扁桃酸对映体

目的建立α-环己基扁桃酸对映体的萃取拆分方法并考察各个影响因素对拆分效果的影响。方法以D-酒石酸酯和β-环糊精为手性选择体来萃取拆分α-环己基扁桃酸对映体。结果考察了酒石酸酯/β-环糊精分离体系中萃取拆分α-环己基扁桃酸对映体的分配行为，着重研究了酒石酸酯烷基链长度、pH值、D-酒石酸酯浓度和β-环糊精浓度对萃取拆分效果的影响。结论D-酒石酸异丁酯与R对映体形成的复合物稳定性比与S对映体形成的好；随着pH值增大，分配比和分离因子都降低；D-酒石酸酯和β-环糊精浓度对萃取拆分的影响较大。     

衍生化GC法测定生物转化产品L-山梨糖及其中残余D-山梨醇的含量

设计了生物转化产品L-山梨糖及其中残余D-山梨醇的衍生化GC测定方法。以乙酸酐—吡啶(1∶1)为衍生化试剂对样品中残余D-山梨醇进行乙酰化GC测定,再以四氢硼钠为还原剂、乙酸酐为乙酰化试剂对样品中L-山梨糖进行还原乙酰化GC测定。结果表明,D-山梨醇及L-山梨糖分别在0.01999～2.999μg及4.00～24.00μg范围内呈线性。本法精密度及回收率均较好,可用于监测L-山梨糖生物转化终点及其成品中L-山梨糖及残余D-山梨醇的含量。     

D-赖氨酸、L-谷氨酰胺和L-酪氨酸对格列美脲及其顺式异构体识别的电喷雾质谱法研究

目的 使用电喷雾质谱技术,研究3种氨基酸（D-赖氨酸、L-谷氨酰胺和L-酪氨酸）作为手性选择探针对格列美脲和格列美脲异构体的识别效应。方法 分别将3种氨基酸与格列美脲及其顺式异构体溶液混合,用电喷雾/离子阱质谱提取非共价结合的复合物,在二级质谱中通过碰撞诱导解离（CID）方法给予不同的碎裂能量,考察碎片离子的丰度从而进行格列美脲及其顺式异构体的识别。结果 L-酪氨酸、D-赖氨酸和L-谷氨酰胺对格列美脲及其顺式异构体均有识别效应,识别率分别为1.61、2.92和2.17。结论 以3种手性氨基酸作为立体异构区分探针,首次实现了格列美脲和格列美脲顺式异构体的质谱法快速识别。     

综合主成分分析法和皮肤电阻法对几种促透剂促透效果的比较

目的 建立一种简单有效的快速评价促透剂透皮吸收促进效果的方法，并比较综合主成分分析法和皮肤电阻法的促透剂评价结果。方法 以氨茶碱作为模型药物，氮酮、薄荷醇、冰片、油酸及其联用作为促透剂，SD大鼠背部离体皮肤作为渗透屏障，HPLC测定接收液中的药物浓度，计算累积渗透量、渗透系数、稳态流量、滞后时间和增渗倍数，运用综合主成分分析法对促透效果进行综合评价；测定在促透剂作用下的大鼠皮肤电阻随时间的变化，评价促透剂对皮肤的作用程度。结果 用Franz扩散池方法结合综合主成分分析法，得到对氨茶碱有促透效果的促透剂有油酸加冰片以及薄荷醇，且油酸加冰片的促透效果大于薄荷醇；用皮肤电阻法测得有促透作用的是油酸加冰片、薄荷醇加氮酮、薄荷醇、氮酮、油酸、冰片加氮酮以及薄荷醇加冰片，且作用程度依次递减。采用皮肤电阻法评价的促透效果与采用体外透皮吸收试验评价的结果基本平行(r=0.886 9)。结论 综合主成分分析法和皮肤电阻法都可以客观评价促透剂的效果，且2种方法具有明显的相关性。     

6-氟-L-多巴合成及其对映纯度测定的研究

目的　合成6-氟-L-多巴(6-FDOPA) ,并测定其对映纯度。方法　以硝基藜芦醛(2)为原料,经亲核取代、还原碘化、手性相转移催化烷基化等多步反应得新化合物2-(2-氟-4,5-二甲氧苄基)-N-(二苯基甲叉)甘氨酸叔丁酯(8) ,8经水解反应制备终产物6-FDOPA ,用手性流动相和反相C₁₈柱的HPLC法测定其对映纯度。结果　合成6-氟-L-多巴总反应时间少于90min ,总产率约为33% ,对映纯度大于95%。结论　可大量合成6-FDOPA ,使自动合成6-[¹⁸F]-L-多巴成为可能。为6-[¹⁸F]-L-多巴的放射化学合成及其对映纯度的测定提供了可靠的技术     

合霉素及其前体消旋-反式-1-对硝基苯-2-氨基-1,3-丙二醇的拆开

合霉素(消旋-I_a)可利用由D(-)-扁桃酸制成的α-乙酰氧基苯乙酰氯作为拆开剂拆开.L(+)-I_a的D(-)-α一乙酰氧基苯乙酸酯在乙醇中首先析出.合霉素前体(消旋-II)于应用(+)-酒石酸单甲酯为拆开剂时,获得L(+)-II的酒石酸单甲酯盐,从母液中分得不纯的D(-)-II.     

反式曲马朵在大鼠肝微粒体O-去甲基代谢中的立体选择性

目的研究反式曲马朵O-去甲基代谢的立体选择性。方法高效毛细管电泳法测定大鼠肝微粒体孵育液中反式曲马朵和O-去甲基曲马朵对映体的浓度,酶促动力学方法研究O-去甲基曲马朵对映体的生成。结果 (-)-O-去甲基曲马朵生成有较大的V_max;反式曲马朵两对映体间存在相互作用,使(+)-O-去甲基曲马朵生成的V_max明显减慢;奎宁及奎尼丁对(+)-O-去甲基曲马朵生成的抑制作用较强。结论反式曲马朵O-去甲基代谢有立体选择性,对映体间的相互作用及酶抑制剂使其立体选择性程度加强。     

多伞阿魏挥发油化学成分GC-MS分析及D-柠檬烯抗胃癌活性研究

目的 分析多伞阿魏新鲜药材挥发油的化学成分,初步探讨D-柠檬烯体外抗胃癌作用。方法 采用GC-MS分析多伞阿魏挥发油的化学成分;采用MTT法检测D-柠檬烯对人胃癌细胞AGS和SGC-7901的增殖抑制作用;采用Hoechst33258荧光染色法观察D-柠檬烯对人胃癌细胞AGS的影响;应用流式细胞仪检测D-柠檬烯对人胃癌细胞AGS凋亡的影响。结果 多伞阿魏挥发油主要的化学成分有α-蒎烯（6.76%）、崁烯（8.38%）、α-月桂烯（4.66%）、3-蒈烯（4.84%）、D-柠檬烯（52.84%）、乙酸龙脑酯（5.24%）等。MTT法检测结果显示,与空白对照组比较,D-柠檬烯对人胃癌细胞AGS和SGC-7901均具有不同程度的增殖抑制作用,呈现剂量依赖关系,其中D-柠檬烯对人胃癌细胞AGS的增殖抑制作用较强,IC₅₀为（0.87±0.05）mmol·L^-1;D-柠檬烯作用于人胃癌细胞AGS后,细胞核被Hoechst 33258染色呈亮蓝色,随着药物浓度的增加蓝色荧光越强;流式细胞凋亡检测结果显示,与空白对照组比较,D-柠檬烯可诱导人胃癌细胞AGS发生凋亡,呈现剂量依赖关系。结论 多伞阿魏挥发油的主要物质基础为单萜类、倍半萜类化合物,其中D-柠檬烯的相对百分含量最高;D-柠檬烯对人胃癌细胞AGS和SGC-7901均具有一定的增殖抑制作用,其中D-柠檬烯对人胃癌细胞AGS的诱导凋亡活性最强。     

毛细管电泳法分离测定血浆样品中盐酸多奈哌齐对映体

目的分离、测定血浆样品中盐酸多奈哌齐对映体的含量。方法建立高效毛细管电泳法血浆中加入内标L-酒石酸布托菲诺后，碱化并以异丙醇-正己烷(3∶97)提取血浆样品，采用未涂层熔融石英毛细管柱(70 cm×50 μm ID)，以25 mmol·L^-1磷酸-三乙胺(pH 2.5)为运行缓冲液，2.5%磺化β-环糊精为手性添加剂，进样电压为-20 kV，进样时间为15 s，运行电压为-20 kV。对盐酸多奈哌齐对映体进行电泳分离，并进行家兔血浆样品中盐酸多奈哌齐对映体定量分析的方法验证。结果在上述电泳条件下，盐酸多奈哌齐对映体可达基线分离。测得血浆样品中R(-)-多奈哌齐的回归方程为：A_s/A_i=0.024 2+0.289 2C，r=0.999 2，S(+)-多奈哌齐的回归方程为：A_s/A_i=0.010 8+0.273 7C，r=0.999 7，线性范围为0.1～5 mg·L^-1，检测限为0.05 mg·L^-1。结论本法与手性柱HPLC法相比，有高效、快速和经济等优点。     

南重楼Paris vietnamensis活性物质的分离与鉴定

目的研究南重楼Paris vietnamensis (Takht.)中具有细胞毒活性的甾体皂苷类化学成分。方法采用柱色谱进行分离纯化，通过光谱分析和理化方法鉴定化合物结构，并进行体外细胞毒活性筛选。结果从南重楼中分离得到11个甾体皂苷类化合物，化合物1结构为：3β,5α,6α-三羟基-7(8)-烯-异螺甾烷醇-3-氧-β-D-葡吡喃糖基(1→3)［α-L-鼠李吡喃糖基(1→2)］-β-D-葡吡喃糖苷(1)，命名为南重楼皂苷A。化合物2～11分别为：25(R)-薯蓣皂苷元-3-氧-α-L-阿拉伯呋喃糖基(1→4)-β-D-葡吡喃糖苷(2)；25(R)薯蓣皂苷元-3-氧-α-L-鼠李糖吡喃基(1→2)-β-D-葡吡喃糖苷(3)；25(R)薯蓣皂苷元-3-氧-α-L-阿拉伯呋喃糖基(1→4)［α-L-鼠李吡喃糖基(1→2)］-β-D-葡吡喃糖苷(4)；25(R)薯蓣皂苷元-3-氧-β-D-葡吡喃糖基(1→3)［α-L-鼠李吡喃糖基-(1→2)］-β-D-葡吡喃糖苷(5)；25(R)薯蓣皂苷元-3-氧-α-L-鼠李吡喃糖基(1→4)-α-L-鼠李吡喃糖基(1→4)［α-L-鼠李吡喃糖基(1→2)］-β-D-葡吡喃糖苷(6)；25(R)偏诺苷元-3-氧-α-L-阿拉伯呋喃糖基(1→4)-β-D-葡吡喃糖苷(7)；25(R)偏诺苷元-3-氧-α-L-鼠李吡喃糖基(1→2)-β-D-葡吡喃糖苷(8)；25(R)偏诺苷元-3-氧-α-L-阿拉伯呋喃糖基(1→4)［α-L-鼠李吡喃糖基(1→2)］-β-D-葡吡喃糖苷(9)；25(R)偏诺皂苷元-3-氧-β-D-葡吡喃糖基(1→3)［α-L-鼠李吡喃糖基(1→2)］-β-D-葡吡喃糖苷(10)；25(R)偏诺苷元-3-氧-α-L-鼠李吡喃糖基(1→4)-α-L-鼠李吡喃糖基(1→4)［α-L-鼠李吡喃糖基(1→2)］-β-D-葡吡喃糖苷(11)，体外筛选表明部分甾体皂苷类化合物具有细胞毒作用。结论化合物1为一新化合物，化合物2，3，6～11均为首次从南重楼中获得。化合物3，4，6，8具有对肝癌HepG2和胃癌SGC-7901的细胞毒活性。     

Effects of enantiomer and isomer permeation enhancers on transdermal delivery of ligustrazine hydrochloride

Enantiomers and isomers, such as D-limonene, L-limonene, and alpha-terpinene, were selected as enhancers. The effects and mechanisms of penetration enhancers on in vitro transdermal delivery of ligustrazine hydrochloride (LH) across hairless porcine dorsal skin were investigated. Transdermal fluxes of LH through porcine skin were determined in vitro by Franz-type diffusion cells. D-limonene, L-limonene, and alpha-terpinene could significantly promote the transdermal fluxes of LH, but no statistical difference (p > 0.05) between them was found. The lag time of L-limonene and alpha-terpinene were 2.55 and 2.20 times compared with that of D-limonene. Fourier transform-infrared (FTIR) was carried out to analyze the effects of enhancers on the biophysical natures of the stratum corneum (SC) and the permeation enhancement mechanism. FTIR spectra revealed that the changes of peak shift and peak area due to C-H stretching vibrations in the SC lipids were associated with the selected enhancers. All of them could perturb and extract the SC lipids to different extent and L-limonene showed obvious changes. Morphological changes of the skin treated with enhancers were monitored by a scanning electron microscope (SEM). The extraction of the SC lipids by the enhancers led to the disruption of SC and the desquamated SC flake. Apparent density (AD) was newly proposed to estimate the desquamated extent of SC flake. The results showed that the enantiomers and isomers enhanced the permeation of LH by pleiotropic mechanisms.     

Effects of Enantiomer and Isomer Permeation Enhancers on Transdermal Delivery of Ligustrazine Hydrochloride

Enantiomers and isomers, such as D-limonene, L-limonene, and α-terpinene, were selected as enhancers. The effects and mechanisms of penetration enhancers on in vitro transdermal delivery of ligustrazine hydrochloride (LH) across hairless porcine dorsal skin were investigated. Transdermal fluxes of LH through porcine skin were determined in vitro by Franz-type diffusion cells. D-limonene, L-limonene, and α-terpinene could significantly promote the transdermal fluxes of LH, but no statistical difference (p > 0.05) between them was found. The lag time of L-limonene and α-terpinene were 2.55 and 2.20 times compared with that of D-limonene. Fourier transform-infrared (FTIR) was carried out to analyze the effects of enhancers on the biophysical natures of the stratum corneum (SC) and the permeation enhancement mechanism. FTIR spectra revealed that the changes of peak shift and peak area due to C-H stretching vibrations in the SC lipids were associated with the selected enhancers. All of them could perturb and extract the SC lipids to different extent and L-limonene showed obvious changes. Morphological changes of the skin treated with enhancers were monitored by a scanning electron microscope (SEM). The extraction of the SC lipids by the enhancers led to the disruption of SC and the desquamated SC flake. Apparent density (AD) was newly proposed to estimate the desquamated extent of SC flake. The results showed that the enantiomers and isomers enhanced the permeation of LH by pleiotropic mechanisms.     

Effects of cinnamene enhancers on transdermal delivery of ligustrazine hydrochloride.

Cinnamene compounds, cinnamic acid, cinnamaldehyde and cinnamic alcohol, were employed as enhancers. The effects and mechanisms of penetration promoters on the in vitro percutaneous absorption of ligustrazine hydrochloride across hairless porcine dorsal skin were investigated. Transdermal fluxes of ligustrazine hydrochloride through porcine skin were determined in vitro by Franz-type diffusion cells. The results indicated that the penetration flux of ligustrazine hydrochloride by cinnamic acid was the greatest. Significant statistical differences (P<0.05) were found between cinnamic acid and other promoters. Fourier transform-infrared (FT-IR) were carried out to analyze the effects of enhancers on the biophysical properties of the stratum corneum and the permeation enhancement mechanisms. FT-IR results revealed that the changes of peak shift and peak area due to C-H stretching vibrations in the stratum corneum lipids were associated with the selected enhancers. All of them could perturb and extract the stratum corneum lipids to different extent. Morphological changes of the skin treated with enhancers were monitored by a scanning electron microscope. It was demonstrated that the extraction of the stratum corneum lipids by the enhancers led to the disruption of stratum corneum and the desquamation of stratum corneum flake. Apparent density was newly proposed to estimate the desquamated extent of stratum corneum flake. Correlation analysis revealed that there was a linear relationship between apparent density and decrease in peak area. The results showed that the permeation enhancement mechanisms of cinnamene were pleiotropic ones, including disordering the lipids, extracting the lipids and competitive hydrogen bonding between cinnamene enhancers and amides of ceramide head groups in stratum corneum.     

Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: a study using TGA, FTIR, TEWL and drug permeation as markers

Vehicles and permeation enhancers (PEs) used in transdermal drug delivery (TDD) of a drug can affect skin hydration, integrity and permeation of the solute administered. This investigation was designed to study the effect of the most commonly used vehicles and PEs on rat skin hydration, barrier function and permeation of an amphiphilic drug, imipramine hydrochloride (IMH). An array of well-established techniques were used to confirm the findings of the study. Thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy were used to determine changes in skin hydration. Alteration of the stratum corneum (SC) structure was investigated using FTIR studies. To monitor the barrier function alteration, transepidermal water loss (TEWL) measurement and permeation studies were performed. Our findings indicate that with hydration, there was an increase in the bound water content of the skin, and pseudoequilibrium of hydration (a drastic decrease in hydration rate) was achieved at around 12 h. Hydration increased the ratio between amide-I and amide-II peaks in FTIR and reduced the C-H stretching peak area. Both propylene glycol (PG) and ethanol (EtOH) dehydrated skin, with the latter showing a predominant effect. Furthermore, it was confirmed that PG and EtOH decreased the bound water content due to alteration in the protein domains and extraction of SC lipids, respectively. The effect of hydration on the SC was found to be similar to that reported for temperature. Permeation studies revealed that the dehydration caused by vehicles decreased IMH flux, whereas the flux was enhanced by PEs. The role of partition was predominant for the permeation of IMH through dehydrated skin. A synergistic effect was observed for PG and menthol in the enhancement of IMH. Further findings provided strong evidence that PG affects protein domains and EtOH extracts lipids from the bilayer. Both PG and EtOH, with or without PEs, increased TEWL. Initial TEWL was well correlated with the flux of IMH through the same skin. It was found that both PG and EtOH affect the permeation of solute and TEWL by dehydration. The experiments also proved that the initial TEWL value has a strong potential as a predictive tool for the permeation of the solute.     

Effect of menthone and related compounds on skin permeation of drugs with different lipophilicity and molecular organization of stratum corneum lipids

The objective of this article was to investigate the enhancing effect of menthone, menthol and pulegone on the transdermal absorption of drugs with different lipophilicity and probe their mechanisms of action at molecular level. Five model drugs, namely osthole, tetramethylpyrazine, ferulic acid, puerarin and geniposide, which were selected based on their lipophilicity denoted by logK_o/w, were tested using in vitro permeation studies in which Franz diffusion cells and rat skin were employed. Infrared spectroscopy and molecular dynamic simulation were used to investigate the effect of these enhancers on the stratum corneum (SC) lipids, respectively. Three compounds could effectively promote the transdermal absorption of drugs with different lipophilicity, and the overall promoting capacities were in the following increasing order: pulegone?<?menthol?<?menthone. The penetration enhancement ratio was roughly in parabolic curve relationships with the drug lipophilicity after treatment with menthol or menthone, while the penetration enhancement effect of pulegone hardly changed with the alteration of the drug lipophilicity. The molecular mechanism studies suggested that menthone and menthol enhanced the skin permeability by disordering the ordered organization of SC lipids and extracted part of SC lipids, while pulegone appeared to promote drug transport across the skin only by extracting part of SC lipids.     

Investigating the potential of essential oils as penetration enhancer for transdermal losartan delivery: Effectiveness and mechanism of action

The effect of tea tree oil (TTO), cumin oil (CO), rose oil (RO) and aloe vera oil (AVO) on the skin permeation of losartan potassium (LP) was investigated. In vitro skin permeation studies were carried out using rat skin. The mechanism of skin permeation enhancement of LP by essential oils treatment was evaluated by FTIR, DSC, activation energy measurement and histopathological examination. Both concurrent ethanol/enhancer treatment and neat enhancer pretreatment of rat SC with all the oils produced significance increase in the LP flux over the control. The effectiveness of the oils as the penetration enhancers was found to be in the following descending order: AVO > RO > CO > TTO. However, only AVO was the only enhancer to provide target flux required to deliver the therapeutic transdermal dose of LP. FTIR and DSC spectra of the enhancer treated SC indicated that TTO, CO, RO and AVO increased the LP permeation by extraction of SC lipids. The results of thermodynamic studies and histopathological examination of AVO treated SC suggested additional mechanisms for AVO facilitated permeation i.e. transient reduction in barrier resistance of SC and intracellular transport by dekeratinization of corneocytes which may be attributed to the presence of triglycerides as constituents of AVO. It is feasible to deliver therapeutically effective dose of LP via transdermal route using AVO as penetration enhancer.     

Investigation into the potential of iontophoresis facilitated delivery of ketorolac

The potential for iontophoresis facilitated transdermal transport of ketorolac was investigated using rat skin. Studies of electrical, physicochemical and device-related factors acting on the permeation kinetics of in vitro iontophoresis were performed. Iontophoresis increased the transdermal permeation flux of ketorolac as compared to the diffusion. Increase in applied current density or decrease in ionic strength of the donor solution enhanced the flux of the drug. Use of either platinum or silver/silver chloride electrodes resulted in similar enhancement of drug flux. Continuous current was more potent than pulsed current in promoting ketorolac transdermal permeation. Increasing the frequency or on:off ratio of pulse current induced an enhancement of the flux through the skin. An increase in donor drug loading dose or increasing the duration of current application resulted in enhancement of the drug flux. Pretreatment of the skin with D-limonene in ethanol or D-limonene in ethanol + ultrasound significantly enhanced the iontophoretic flux of the drug in comparison to passive flux with or without pretreatment. Trimodality treatment comprising of pretreatment with D-limonene in ethanol + ultrasound in combination followed by iontophoresis was found to be most potent for enhancing the rate of permeation of ketorolac.     

Thermotropic and spectroscopic behavior of skin: relationship with percutaneous permeation enhancement

Stratum corneum (SC) is comprised of lipids, protein and low molecular weight water-soluble components. Changes in these skin micro constituents can be understood by instrumental methods like differential scanning calorimetry (DSC) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. The former provides information about changes in thermotropic behavior of SC lipids and proteins, whereas the latter provides data about alterations at molecular and conformational level. Most of the DSC thermograms of intact mammalian SC show two reversible and two irreversible transitions in the temperature range of 25-125 degrees C. The reversible endotherms are ascribed to lipid melting transitions, whereas the irreversible endotherms are ascribed to protein denaturation. Similarly, the FTIR spectral bands of SC occurring between 2920-2850 cm-1 and between 1650-1550 cm-1 have been suggested to arise from lipid and protein molecular vibrations, respectively. Treatment of skin with solvents or permeation enhancers alters the composition of lipids or their molecular arrangement in the skin microenvironment, which leads to changes in permeability of drug molecules. Furthermore, inhibition of lipid synthesis in epidermis with concomitant decrease in enthalpy of lipid endothermic transitions and reduction in height and area of asymmetric and symmetric C-H stretching peaks have been found to be directly correlated with enhanced permeation of drugs. In addition, method of skin preparation, type of skin, types of enhancer etc. also influence both the nature and intensity of responses recorded in spectrographs and thermograms. Therefore, the modification in spectrographs and thermograms of skin samples treated with various enhancers, vehicles etc. are expected to provide better insight into their mechanism of action on the skin. This review article shall critically evaluate the thermotropic and infrared spectroscopic data of SC/epidermis after various treatments.     

在裸小鼠皮肤上松节油对双氯芬酸钠的渗透动力学研究

目的以双氯芬酸钠为模型药物,研究松节油对药物的透皮吸收促透作用.方法采用氮酮、松节油对皮肤预处理的方法,通过离体裸小鼠皮肤渗透释药实验,不同时间取样,测定接受液中双氯芬酸钠的浓度,计算累积透过量、稳态流量、渗透系数和滞后时间等指标.结果松节油对双氯芬酸钠促透作用较氮酮弱,但其时滞较氮酮短(P<0.05).两种促透剂均减弱双氯芬酸钠的储库效应,其中松节油减弱程度没有氮酮大;两种促透剂对双氯芬酸钠的时滞均有延长,松节油延长更明显(P<0.05).结论松节油对双氯芬酸钠有一定的促透作用.     

Mechanism of Transport Enhancement of LHRH Through Porcine Epidermis by Terpenes and Iontophoresis: Permeability and Lipid Extraction Studies

Purpose. The purpose of this study was to investigate the effect of 5% terpenes (i.e., limonene, carvone, thymol, and cineole)/ethanol (EtOH) and iontophoresis on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through the porcine epidermis and biophysical changes in the stratum corneum (SC) lipids by fourier transform infrared (FT-IR) spectroscopy. Methods. The porcine epidermis was pretreated with enhancer for 2 h. The permeability measurement system included Franz diffusion cells, Ag/AgCl electrodes, and SCEPTOR^® iontophoretic power source. FT-IR spectroscopy was performed to assess the possible contribution of lipid extraction to the transport enhancement of LHRH. Results. Terpenes in combination with EtOH significantly (p < 0.05) increased the flux of LHRH in comparison with the control (epidermis which was not enhancer treated). Iontophoresis further enhanced (p < 0.05) the flux of LHRH through terpenes/EtOH treated epidermis in comparison with their passive permeability. Reversibility studies showed that the post-recovery passive flux of LHRH through 5% limonene in EtOH/iontophoresis treated epidermis was significantly (p < 0.05) decreased but did not significantly recover to the baseline flux (i.e., flux through control epidermis). The SC treated with terpenes/ EtOH showed a decrease in peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison to untreated SC. A greater percent decrease in peak heights and areas was obtained by limonene/EtOH. However, treatment of the SC with terpenes/EtOH followed by iontophoresis did not further decrease the percentage of peak height and area over and above terpene/EtOH suggesting that iontophoresis alone does not cause SC lipid extraction. Conclusions. Terpenes/EtOH increased LHRH permeability by enhancing the extraction of the SC lipids. Iontophoresis synergistically enhanced the permeability of LHRH through terpenes/EtOH treated epidermis. Thus, terpenes can be used as chemical enhancers in combination with iontophoresis to enhance the transdermal delivery of peptides such as LHRH.