Protopine

353.37

353.37

204-999-6

UIW569HT35

DTXSID90156282

Monoclinic prisms from alcohol + chloroform

29391900

57.2

2.8

Solid

1.399 g/cm³

208 °C

486.8°C (rough estimate)

284.9±29.8 °C

1.5800 (estimate)

soluble in 15 parts chloroform, 900 parts alcohol, 1000 parts ether; slightly soluble in ethyl acetate, carbon disulfide, benzene, petroleum ether

Refrigerator

6.36X10-10 mm Hg at 25 deg C (est)

Henry's Law constant = 2.85X10-16 atm-cu m/mol at 25 °C (est)

178.3 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated]

Twinned crystals from methanol, decomposes at 217 °C /Protopine methiodide/|Prisms from alcohol; soluble in 143 parts water at 13 °C; soluble in alcohol /Protopine hydrochloride/|Needles from water /Protopine hydrochloride hexahydrate/|Hydroxyl radical reaction rate constant = 1.91X10-10 cu cm/molecule-sec at 25 °C (est)

III

6.1(b)

1544

24/25

VS2800000

Stable under recommended storage conditions.

P301 + P310 + P330

H301

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents

|Danger|H301 (33.33%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P301+P312, P321, P330, P405, and P501|Aggregated GHS information provided by 6 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Skin protection: Handle with gloves.|Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.|Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.|Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

IDENTIFICATION AND USE: Protopine is a solid. It is used as medication. HUMAN EXPOSURE AND TOXICITY: Using gene reporter assays performed in transiently transfected HepG2 cells, it was demonstrated that the induction of CYP1A1 expression by protopine was associated with mild or negligible activation of the aryl hydrocarbon receptor. CYP1A mRNA levels induced by protopine in both HepG2 cells and human hepatocytes did not result in elevated CYP1A protein or activity levels. ANIMAL STUDIES: Protopine showed an ability to enhance gamma-aminobutyric acid binding to rat brain synaptic membrane receptors in in vitro radiolabeling studies. Protopine has antiarrhythmic effects and may directly inhibit rapid electrical activity of cardiac cells.

The antiarrhythmic effects of protopine on experimental arrhythmia were studied in various animals. Protopine elevated the dose of aconitine needed to induce VP, VT, and VF in rats and increased the dose of strophanthin (strophanthine K) that induced VP in guinea pigs. It also shortened the duration of central arrhythmia induced by aconitine and the duration of arrhythmia induced by benzene-epinephrine (adrenaline) in rats. It prevented rats and mice from developing arrhythmia induced by intravenous calcium chloride and inhalation of chloroform, respectively. In rabbits, the drug raised VFT. It was concluded that protopine has antiarrhythmic effects and may directly inhibit rapid electrical activity of cardiac cells.

LD50 Guinea pig ip 116 mg/kg|LD50 Guinea pig oral 237 mg/kg|LD50 Mouse ip 482 mg/kg

Protopine is derived from opium. It is also from the herb Fumaria officinalis L, Chelidonium majus L, and many other Papaveraceae and Fumariaceae(1).

Protopine's production and use in biomedical research(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.2X10+4(SRC), determined from a structure estimation method(2), indicates that protopine is expected to be immobile in soil(SRC). The estimated pKa of protopine is 4.95(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of protopine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.8X10-16 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Protopine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.4X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2016).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.2X10+4(SRC), determined from a structure estimation method(2), indicates that protopine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.8X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 24(SRC), from an estimated log Kow of 3.47(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2016).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), protopine, which has an estimated vapor pressure of 6.4X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2)), is expected to exist solely in the particulate phase. Particulate-phase protopine may be removed from the air by wet and dry deposition(SRC). Protopine contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Protopine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Protopine contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 24 was calculated in fish for protopine(SRC), using an estimated log Kow of 3.47(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of protopine can be estimated to be 1.2X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that protopine is expected to be immobile in soil. The estimated pKa of protopine is 4.95(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The Henry's Law constant for protopine is estimated as 2.9X10-16 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that protopine is expected to be essentially nonvolatile from water and moist soil surfaces(2). Protopine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.4X10-10 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to protopine may occur through inhalation and dermal contact with this compound at workplaces where protopine is produced or used. Limited monitoring data indicate that the general population may be exposed to protopine via ingestion of poppy seeds and a few herbs containing protopine. (SRC)

Analgesics, Opioid; Histamine H1 Antagonists; Platelet Aggregation Inhibitors|/EXPL THER/ ... In the present study, we studied the anticancer proliferation and adhesion effects of five alkaloids which were isolated from Corydalis yanhusuo. MTT dose response curves, cell migration assay, cell invasion assay, as well as three types of cell adhesive assay were performed on MDA-MB-231 human breast cancer cells. The mechanism of the compounds on inhibiting heterotypic cell adhesion were further explored by determining the expression of epidermal growth factor receptor (EGFR), Intercellular adhesion molecule 1 (ICAM-1), alphav-integrin, beta1-integrin and beta5-integrin by western blotting assay. In five tested alkaloids, only protopine exhibited anti-adhesive and anti-invasion effects in MDA-MB-231 cells, which contributed to the anti-metastasis effect of Corydalis yanhusuo. The results showed that after treatment with protopine for 90 min, the expression of EGFR, ICAM-1, alphav-integrin, beta1-integrin and beta5-integrin were remarkably reduced. The present results suggest that protopine seems to inhibit the heterotypic cell adhesion between MDA-MB-231 cells, and human umbilical vein endothelial cells by changing the expression of adhesive factors.|/EXPL THER/ ... In this study, we investigated whether protopine derived from Hypecoum erectum L could suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages (Raw 264.7 cells). Protopine was found to reduce nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E(2) (PGE(2)) production by LPS-stimulated Raw 264.7 cells, without a cytotoxic effect. Pre-treatment of Raw 264.7 cells with protopine reduced the production of pro-inflammatory cytokines. These inhibitory effects were caused by blocking phosphorylation of mitogen-activated protein kinases (MAP kinases) and also blocking activation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB).|/EXPL THER/ In this study, we investigated the anticancer effect of protopine on human hormone-refractory prostate cancer (HRPC) cells. Protopine exhibited an anti-proliferative effect by induction of tubulin polymerization and mitotic arrest, which ultimately led to apoptotic cell death. The data suggest that protopine increased the activity of cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex and that contributed to cell apoptosis by modulating mitochondria-mediated signaling pathways, such as Bcl-2 phosphorylation and Mcl-1 down-regulation. In conclusion, the data suggest that protopine is a novel microtubule stabilizer with anticancer activity in HRPC cells through apoptotic pathway by modulating Cdk1 activity and Bcl-2 family of proteins.|For more Therapeutic Uses (Complete) data for PROTOPINE (12 total), please visit the HSDB record page.

Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood. (See all compounds classified as Histamine H1 Antagonists.)|Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. (See all compounds classified as Analgesics, Opioid.)|Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. (See all compounds classified as Platelet Aggregation Inhibitors.)

Xiang-Fu-Si-Wu Decoction (XFSWD) has been widely used to treat primary dysmenorrhea in clinical practice for hundreds of years and shown great efficacy. One fraction of XFSWD, which was an elution product by macroporous adsorption resin from aqueous extract solution with 60% ethanol (XFSWE), showed great analgesic effect. The present study was conducted to investigate the possible pharmacokinetic and tissue distribution profiles of four major bioactive constituents (berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine) after oral administration of XFSWE in dysmenorrheal symptom rats, and to compare the difference between normal and dysmenorrheal symptom rats. Estradiol benzoate and oxytocin were used to produce dysmenorrheal symptom rat model. The experimental period was seven days. At the final day of experimental period, both normal and dysmenorrheal symptom rats were orally administrated with XFSWE, and then the blood and tissues samples were collected at different time points. Berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine in blood and tissue samples were determined by LC-MS/MS. Pharmacokinetic parameters were calculated from the plasma concentration-time data using non-compartmental methods. The differences of pharmacokinetic parameters among groups were tested by one-way analysis of variance (ANOVA). There were statistically significant differences (P<0.05) in Cmax, Tmax, AUC(0-t), AUC(0-infinity), MRT(0-t), MRT(0-infinity) and CL/F between normal and dysmenorrheal symptom rats that orally administered with same dosage of XFSWE. In tissue distribution study, the results showed that the overall trend was C(Spleen)>C(Liver)>C(Kidney)>C(Uterus)>C(Heart)>C(Lung)>C(Ovary)>C(Brain)>C(Thymus), C(M-60 min)>C(M-120 min)>C(M-30 min)>C(C-60 min)>C(C-120 min)>C(C-30 min). The contents of protopine in liver, spleen and uterus were more than that in other tissues of dysmenorrheal symptom rats. Compared to normal rats, partial contents of the compounds in dysmenorrheal symptom rats' tissues at different time points had significant difference (P<0.05). This study was the first report about pharmacokinetic and tissue distribution investigation in dysmenorrheal symptom animals. The results indicated that berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine have higher uptake and slower elimination in the rats with dysmenorrheal syndrome, which suggests that the rate and extent of drug metabolism were altered in dysmenorrheal syndrome rats. And the results also demonstrated that berberine, protopine and tetrahydropalmatine in normal and dysmenorrheal symptom rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in dysmenorrheal symptom animals.

Eschscholtzia californica preparations are in use as phytopharmaceuticals and as herbal drugs. Studies are described on the metabolism and the toxicological analysis of the Eschscholtzia californica alkaloids californine and protopine in rat urine using gas chromatography-mass spectrometry. ... Protopine ... undergoes extensive demethylenation of the 2,3-methylenedioxy group followed by catechol-O-methylation. All phenolic hydroxy metabolites were found to be partly conjugated. The authors' systematic toxicological analysis procedure using full-scan gas chromatography-mass spectrometry after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of the main metabolites of californine and protopine in rat urine after a dose which should correspond to that of drug users. Therefore, use of Eschscholtzia californica preparations should also be detectable in human urine by the authors' systematic toxicological analysis procedure.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ALTERNATIVE and IN VITRO TESTS/ In this study, we investigated the anticancer effect of protopine on human hormone-refractory prostate cancer (HRPC) cells. Protopine exhibited an anti-proliferative effect by induction of tubulin polymerization and mitotic arrest, which ultimately led to apoptotic cell death. The data suggest that protopine increased the activity of cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex and that contributed to cell apoptosis by modulating mitochondria-mediated signaling pathways, such as Bcl-2 phosphorylation and Mcl-1 down-regulation. In conclusion, the data suggest that protopine is a novel microtubule stabilizer with anticancer activity in HRPC cells through apoptotic pathway by modulating Cdk1 activity and Bcl-2 family of proteins.|/ALTERNATIVE and IN VITRO TESTS/ The isoquinoline alkaloids protopine and allocryptopine are present in phytopreparations from medicinal plants, such as Fumaria officinalis. Since nothing is known about effects of the alkaloids on the expression of xenobiotic-metabolizing enzymes, we examined whether protopine or allocryptopine affect the expression of cytochromes P450 (CYPs) 1A1 and 1A2 in primary cultures of human hepatocytes and human hepatoma HepG2 cells. In HepG2 cells, protopine and allocryptopine significantly increased CYP1A1 mRNA levels after 24 hr exposure at concentrations from 25 and 10 uM, respectively, as shown by real-time PCR. Both protopine and allocryptopine also dose-dependently increased CYP1A1 and CYP1A2 mRNA levels in human hepatocytes. However, the effects of the tested alkaloids on both cell models were much lower than the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a prototypical CYP1A inducer. Using gene reporter assays performed in transiently transfected HepG2 cells, we demonstrated that the induction of CYP1A1 expression by either protopine or allocryptopine was associated with mild or negligible activation of the aryl hydrocarbon receptor. In contrast to TCDD, CYP1A mRNA levels induced by protopine or allocryptopine in both HepG2 cells and human hepatocytes did not result in elevated CYP1A protein or activity levels as shown by western blotting and EROD assays, respectively. ...

4,6,7,14-tetrahydro-5-methyl-bis(1,3)benzodioxolo(4,5-c-5',6'-g)azecin-13(5H)-one

From Papaver radicatum Rottb., the alkaloids protopine, beta-allocryptopine, cryptopine, amurensinine, O-methylthalisopavine, amurine, berberine, sanguinarine and papaverrubine E were isolated by column chromatography and identified by thin layer chromatography. Thin layer chromatography also revealed the presence of 2 other alkaloids which could not be identified.|In this study, we introduced a simple and sensitive method of capillary electrophoresis with ultraviolet light-emitting diode-induced native fluorescence (UV-LEDIF) detection for the determination of isoquinoline alkaloids in extracts of Chelidonium majus L. Samples were extracted with acidic methanol and the extracts were directly analyzed by CE. Simultaneous determination of protopine, chelidonine, coptisine, sanguinarine, allocryptopine, chelerythrine and stylopine was performed in 20 mM phosphate buffer (pH 3.1). The baseline separation of these alkaloids was finished within 20 min. As these alkaloids have native fluorescence, they were directly detected using the commercially available UV light emitting diode without troublesome fluorescent derivatization. Satisfactory LOD values were obtained for the studied compounds considering their appearance in natural extracts. Lower limits of detection were 0.05 ug/mL for protopine ... . The developed method was successfully applied to determine the contents of seven alkaloids in the aerial parts of Chelidonium majus L, which varied from 0.025 to 0.763% (w/w). ...

Eschscholtzia californica preparations are in use as phytopharmaceuticals and as herbal drugs. Studies are described on the metabolism and the toxicological analysis of the Eschscholtzia californica alkaloids californine and protopine in rat urine using gas chromatography-mass spectrometry. ... Protopine ... undergoes extensive demethylenation of the 2,3-methylenedioxy group followed by catechol-O-methylation. All phenolic hydroxy metabolites were found to be partly conjugated. The authors' systematic toxicological analysis procedure using full-scan gas chromatography-mass spectrometry after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of the main metabolites of californine and protopine in rat urine after a dose which should correspond to that of drug users. Therefore, use of Eschscholtzia californica preparations should also be detectable in human urine by the authors' systematic toxicological analysis procedure.|A sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method has been developed and validated for the simultaneous quantification of tetrahydropalmatine, protopine and palmatine in rat plasma using phenacetin as the internal standard (IS). Two hundred microliters plasma samples were extracted by dichloromethane under a strong basic condition. The analytes were separated by a C18 column and detected with a single quadrupole mass spectrometer. The used mobile phase was acetonitrile-water (40:60, v/v) containing 5 mM ammonium acetate and 0.2% glacial acetic acid. Detection was carried out by positive electrospray ionization in selected ion reaction (SIR) mode at m/z 356.6 for tetrahydropalmatine, 354.6 for protopine, 352.6 for palmatine and 180.4 for the IS, respectively. The method was validated over the concentration range of 1.00-500 ng/mL and the lower limit of quantification (LLOQ) was 1.00 ng/mL for all three analytes. The intra- and inter-day precision values were less than 9% relative standard deviation (R.S.D.), and the relative error ranged from -7.4 to 4.8%. The extraction /recovery was/ on average ... 84.75% ... . The validated method was successfully applied to a pharmacokinetic study of tetrahydropalmatine, protopine and palmatine in rats after oral administration of Rhizoma Corydalis Decumbentis extract.|/The objective of the study was/ to establish an everted intestinal sac method for determining absorption ingredients of yuanhuzhitong pill and study absorption characteristics of major chemical constituents of yuanhuzhitong pill. The everted intestinal sac model was adopted. Intestinal sac fluid samples at different time points after administration of three concentrations of Yuanhuzhitong pill were collected and determined by HPLC. The accumulative absorbed doses of active constituents were calculated, while the proportion between samples of yuanhuzhitong pill and absorption ingredients was compared. Eight ingredients of Yuanhuzhitong pill can be detected in intestinal sac, they are protopine, palmatine, coptisine, imperatorin, berberine, byakangelicin, alpha-allocryptopine and tetrahydropalmatine. The absorption rate constants (Ka) of eight constituents increased in jejunum and ileum with the increase in concentration of Yuanhuzhitong pill extracts (P < 0.05), indicating a passive absorption. ...|The herbal ingredients of isocorydine and protopine were isolated from Dactylicapnos scandens. This study was aimed at developing a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method to quantify isocorydine and protopine in rat plasma and tissues for pharmacokinetic, tissue distribution and excretion studies. Biological samples were processed with ethyl acetate extraction, and corydaline was chosen as the internal standard (IS). The analytes were separated by a C(18) column and detected with a triple quadrupole mass spectrometer using positive ion ESI in the multiple reaction monitoring (MRM) mode. The MS/MS ion transitions monitored were m/z 342.0 --> 278.9 for isocorydine, 354.1 --> 188.0 for protopine and 370.0 --> 192.0 for IS, respectively. Excellent linearity was observed over the concentration range between 10 and 3000 ng/mL for isocorydine and 10-300 ng/mL for protopine. The lower limit of quantification (LLOQ) was 10 ng/mL for both isocorydine and protopine. This novel method was rapid, accurate, high sensitive and high selective. It was successfully applied to the pharmacokinetic, tissue distribution and excretion studies of D. scandens. ...|Tetrahydropalmatine (THP), dehydrocorydaline (DHC) and protopine are three major bioactive molecules in Rhizoma Corydalis. In this study, a simple and reliable HPLC method was developed for simultaneous analysis of THP, DHC and protopine in rat tissues after gastric gavage administration of Rhizoma Corydalis.