Role of Gabanergic and, or Serotonergic in the Anti-seizure Activity of Methanol Extract of Crinum jagus (J. Thomps) in Experimental Mice

Objective: Crinum jagus is used in traditional African medicine in the treatment of epilepsy, pain and inflammations. Methods: Anticonvulsant activity was investigated using picrotoxin (PCT) and strychnine (STR) tests in experimental paradigm. Results: Crinum jagus leaf methanol extract (200, 400, and 800?mg?kg?1) potentiated hexobarbitone-induced sleeping time and significantly (p<0.05) shortened the duration of convulsions in PCT-induced seizures. Delay in the onset of convulsions in PCT-induced seizure were very significant (p<0.05). Reduction in the frequency of seizures was also significant (p<0.05) in the test. Diazepam (5?mg?kg?1) was used as reference anticonvulsant drugs in the experimental models. While, CJB failed to protect the animals against picrotocin-induced convulsion. Neither the extract of CJL nor CJB confer significant effect on STR-induced convulsion. Flumazenil (GABA receptor antagonist) and cyproheptadine (5-HT2 receptor antagonist) blocked the effect of CJL extract in the PCT tests significantly suggesting that Crinum jagus may be acting by enhancing the effects of the GABAergic and serotonergic systems. Conclusion: The data obtained suggest that methanol leaf extract of C. jagus possessed significant anticonvulsant effect, thereby confirming the traditional uses of C. jagus in the treatment of epilepsies; mechanisms of which may involve interaction with GABAergic and serotonergic pathway.

Pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration / 中国中药杂志

This study aims to establish a rapid and sensitive UPLC-MS/MS method for simultaneously determining the content of strychnine and paeoniflorin in plasma and brain tissue of rats, and compare the pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration. Compared with those in the toxic-dose strychnine group, the AUC_(0-t), AUC_(0-∞), and C_(max) of strychnine decreased by 51.51%, 45.68%, and 46.03%, respectively(P<0.01), and the corresponding values of paeoniflorin increased by 91.41%, 102.31%, and 169.32%, respectively(P<0.01), in the compatibility group. Compared with the normal-dose strychnine group, the compatibility group showed insignificantly decreased C_(max), AUC_(0-t), and AUC_(0-∞) of strychnine, increased C_(max) and T_(max) of paeoniflorin(P<0.01), 66.88% increase in AUC_(0-t), and 70.55% increase in AUC_(0-∞) of paeoniflorin. In addition, the brain tissue concentration of strychnine decreased and that of paeoniflorin increased after compatibility. The combination of paeoniflorin with normal dose and toxic dose of strychnine can inhibit the percutaneous absorption of strychnine, and greatly promote the percutaneous penetration of paeoniflorin, whereas the interaction mechanism remains to be explored. The UPLC-MS/MS method established in this study is easy to operate and has good precision. It is suitable for in vivo study of pharmacokinetic behavior and brain tissue distribution of paeoniflorin and strychnine after percutaneous administration in rats, which provides reference for the safe and rational clinical use of strychnine and the combined use of drugs, and lays a solid foundation for the development of external preparations containing Strychni Semen.

Comparison of three lod determination approaches in tlc / 中国药学杂志

OBJECTIVE: To compare the limits of detection ( LODs) of TLC obtained with three evaluation approaches in Chinese Pharmacopoeia 2015, and facilitate selection of LOD evaluation approach in TLC method validation. METHODS: After development, the spots of strychnine, berberine hydrochloride, and ten chemical dyes were first detected by human eyes and then scanned by thin layer scanner to obtain the LODs based on visual evaluation, signal-to-noise, and standard deviation of the response and the slope. RESULTS: The LODs obtained by the three approaches showed no significant difference. For strychnine and 10 chemical dyes, the LODs based on the three approaches were close to each other. For berberine hydrochloride, the LOD obtained by visual evaluation was slightly lower than those obtained by the other two approaches. CONCLUSION: All the three approaches are feasible to determine LOD in TLC. The approach based on visual evaluation is rapid and reliable, which might be the first choice for LOD determination in TLC.

Study on transport mechanism of brucine and strychnine in MDCK-MDR1 cell monolayer model / 中草药

Objective: To study the bi-direction transport behavior of brucine and strychnine in the MDCK-MDR1 cell monolayer model. Methods: MTT method was employed to confirm the safe concentration of brucine and strychnine towards MDCK-MDR1 cells. The effects of transport time, drug concentration, and P-glycoprotein inhibitor verapamil on cumulative absorption concentration (Ccum) and apparent permeability coefficient (Papp) of brucine and strychnine in MDCK-MDR1 monolayer cells were studied. Results: The Papp value of brucine and strychnine was larger than 1 × 10-5 cm/s and the ratio of Papp(BL→AP) vs Papp(AP→BL) was less than 2. Brucine/ strychnine combined with verapamil decreased the ratio of Papp(BL→AP) vs Papp(AP→BL). Conclusion: The absorption of brucine and strychnine in MDCK-MDR1 cell monolayer model was well and the passive transference was its main intestinal absorption mechanism. The P-gp inhibitor verapamil has a significant inhibitory effect on brucine and strychnine absorption. Brucine and strychnine may be a substrate of P-glycoprotein.

Pharmacokinetic study of procesed Strychni Semen in normal rats / 中草药

Objective: To study the pharmacokinetics and tissue distribution of procesed Strychni Semen in rats after multiple administration at clinical dose. Methods: The rats were given procesed Strychni Semen by intragastric administration for single and several times. The plasma concentrations of brucine and strychnine in plasma and tissues of rats were determined by UPLC-Q-Orbitrap HRMS method, and the organizational distribution differences were compared to explore whether there was accumulation in the body. Results: After single intragastric administration of procesed Strychni Semen, the main pharmacokinetic parameters of brucine and strychnine were as follow: t1/2 was 10.59 and 8.39 h, tmax was 0.77 and 0.64 h, t1/2Ka was 5.38 and 2.63 h, Cmax was 2.97 and 10.83 ng/L, AUC0-t was 87.36 and 172.24 ng∙h/L, CL/F was 40 637.08 and 38 370.26 L/(h∙kg); Brucine and strychnine in processed Strychni Semen reached a steady state after 3 d of administration in rats. After the last administration, the main pharmacokinetic parameters of brucine and strychnine in rats were as follow: t1/2 was 7.07 and 4.75 h, tmax was 0.48 and 0.46 h, t1/2Ka was 3.23 and 1.09 h, Cmax is 5.77 and 34.83 ng/L, AUC0-t was 32.80 and 107.86 ng∙h/L, and CL/F was 75 920.52 and 43 871.54 L/(h∙kg). Compared with the single administration, the content of brucine and strychnine in the liver and kidney tissues was significantly reduced after multiple administrations, and there was no significant change in other tissues. Conclusion: The pharmacokinetics of brucine and strychnine in healthy rats is consistent with one-compartment model. Both of them have the pharmacokinetic characteristics of fast absorption in rats. After 3 d of administration, the serum concentrations of brucine and strychnine reached steady state, and the blood concentration was increased continuously with the increase of administration times. The content of each tissue did not increase after single and multiple administrations. It is suggested that long-term administration of brucine and strychnine will not cause the superposition of the concentration of brucine and strychnine in the blood of rats, which may lead to the occurrence of poisoning.

Anxiolytic Action of Taurine via Intranasal Administration in Mice

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine’s effect on anxiety. For the characterization of potential mechanism of taurine’s anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine’s anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.

Tissue distribution study of strychnine, brucine and their metabolites in rat tissue by LC-MS/MS / 中国药理学通报

Aim: To establish an LC-MS/MS method to simultaneously determinate strychnine (STR), brucine (BRU), strychnine N-oxide(SNO) and brucine N-oxide(BNO) in rat tissue, and study their tissue distributions following single intragastric administration of total alkaloids from Semen Strychni at normal and high toxic dose. Methods: Ephedrine hydrochloride was used as the internal standard (IS). Analytes were extracted from tissue samples using liquid-liquid extraction with chloroform. Chromatographic separations were performed on a ZORBAX E-clipse XDB-C18 column(2.1 x 150 mm, 3. 5 μm) with the mobile phase of phase A(water, 10 mM ammonium acetate, adjusted to pH 4. 0 with formic acid) and B(methanol) at a flow rate of 0. 2 mL · min-1. The column temperature was maintained at 30 °C. Mass spectrometric detection was performed on an API4000+ triple quadrupole mass spectrometer equipped with an electrospray ionization (ESI) interface in the positive ion multiple reaction monitoring(MRM) mode. Results: Excellent linearity was observed in all analytes within their linear ranges. In-tra-and inter-day relative standard deviations (RSDs) were less than 14.90%, and accuracies were (85.94 ±1.43)% -(113. 77 ±5.19)%. STR, BRU and SNO distributed in all the tissues in different degree, among which content in kidney and liver was the richest. STR and BRU distributions were low in brain. Conclusions: The developed method is simple, sensitive, specific and reliable, which is suitable for simultaneous determination of STR, BRU, SNO and BNO in rat tissues.

Pharmacokinetics study of brucine and strychnine in rat liver microsomes under different chemical environments / 中草药

Objective To study the enzyme kinetics of brucine (BRU) and strychnine (STR), total alkaloids, and monomers active components of BRU and STR in extracts of Strychnos nux-vomica in rat liver microsomes, and investigate metabolic differences between BRU and STR monomer, total alkaloids, and BRU and STR in extracts in rat liver microsomes. Methods The contents of BRU and STR in the monomers, total alkaloids, and extracts in the metabolic system in vitro were measured by LC-MS/MS method, and the kinetic parameters of the enzyme were calculated. Results Compared with monomer group, Km and Vmax value of BRU and STR in total alkaloids and extracts of S. nux-vomica were obviously decreased; Compared with total alkaloids, Km and Vmax value of BRU and STR monomers in S. nux-vomica were obviously increased. The CLint of BRU among total alkaloids and monomer extracts groups had no significantly difference; And the CLint of STR in three groups was successively decreased. Conclusion Total alkaloids, BRU and STR in S. nux-vomica extracts, and BRU and STR monomer can be metabolized by the liver microsomes, and the pharmacokinetical parameters of BRU and STR in all groups have significant differences in metabolism.

Study on preparation and evaluation in vitro of TASS-LLCN / 中草药

Objective To prepare a new kind of preparation formulation of the total alkaloids from seed of Strychni Semen (TASS), by which could improve their drug loading content and the transdermal function. Methods TASS-LLCN were prepared by hot solvent and high pressure homogeneous method. Using encapsulation efficiency (EE) measured by ultrafiltration as index, the prescription of TASS-LLCN was optimized by response surface methodology with central composite design, and the basic properties of the optimized TASS-LLCN was evaluated. The Franz diffuser method was used to compare the transdermal capacity of both LLCN gel and ordinary gel of TASS. Results The best prescription of TASS-LLCN was as follow: the content of glycerin monooleate (GMO) was 1 403.19 mg/mL, the ratio between GMO and F127 was 7.25:1, the drug loading content was 9.48% and the predicted encapsulation efficiency was 64.01%. The evaluation of basic properties of the optimized TASS-LLCN showed that the average grain diameter was about 186 nm, zeta potential was -33.1 mV, pH was 6.83, the stability was good. The transdermal experiment in vitro showed that the cumulate osmotic quantities in 24 h and the permeation rate of TASS-LLCN gel were both better than ordinary gel of TASS, which had obvious discrepancy (P < 0.05) and showed that LLCN could promote the absorption of active components; the skin retention volume of LLCN gel was still bigger than ordinary gel, which showed that LLCN gel of TASS could store in the skin and release the drug sustainedly. Conclusion TASS-LLCN could obviously enhance the drug loading content and the transdermal function. It is a potential new kind of preparation formulation which have the sustainable effect.

Determination of six constituents in Shiyifang Vinum by HPLC / 中成药

AIM To establish an HPLC method for the content determination of six constituents in Shiyifang Vinum (Notoginseng Radix et Rhizoma,Dipsaci Radix,Carthami Flos,etc.).METHODS The content determination of notoginsenoside R1,ginsenoside Rg1,ginsenoside Rb1 and asperosaponin Ⅵ was performed on a 30℃ thermostatic Inertsil(R) ODS-3 C18column (4.6 mm ×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％ phosphoric acid flowing at 1.0 mL/min in a gradient manner,and the detection wavelength was set at 203 nm.The content determination of brucine and strychnine was conducted on a 30 ℃ thermostatic Geminni(R) C18 110(A) column (4.6 mm × 250 mm,5 μm),with the mobile phase comprising of acetonitrile-mixed solution of 0.01 mol/L sodium heptanesulfonate and 0.02 mol/L potassium dihydrogen phosphate flowing at 1.0 mL/min in an isocratic elution manner,and the detection wavelength was set at 260 nm.RESULTS Six constituents showed good linear relationships within their own ranges (r ＞ 0.999 0),whose average recoveries were 98.52％-99.96％ with the RSDs of 2.0％-2.3％.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Shiyifang Vinum.

Simultaneows Determination of Strychnine and Brucine in Shiyifang Vinum by LC-MS/MS / 中国药师

Objective:To develop a determination method for strychnine and brucine in Shiyifang vinum by LC-MS/MS. Meth-ods:The samples were separated on an Agilent Zorbax SB-C18column(2.1 mm×100 mm,3.5 μm). The mobile phase was metha-nol-10 mmol·L-1ammonium formate solution (adjusting pH to 3.0 with methane acid)(25: 75), and the flow rate was 0.2 ml· min-1. The eletrospray ionization( ESI) with positive source of the mass spectrometer and multiple reaction monitor( MRM) mode were used to detect strychnine(m/z 395.2→243.8;m/z 395.2→212.8)and brucine(m/z 335.2→183.9;m/z 335.2→155.9). Re-sults:The linear range of strychnine was 0.242-7.733 μg·ml-1,and that of brucine was 0.302-9.661 μg·ml-1. The average re-covery was 100.1% (RSD=0.8%,n=6) and 99.4% (RSD=1.4%,n=6),respectively. Conclusion:The method is simple and accurate,which can be used to determine the contents of strychnine and brucine in Shiyifang vinum.

Study on Improving Quality Standard of Qiwei Maqianzi Pills / 中国药房

OBJECTIVE:To improve the quality standard for Qiwei maqianzi pills.METHODS:TLC was used for the qualitative identification of Chebulae Fmctus and Aucklandiae Radix in the preparation.HPLC method was used for the content determination of hydroxy safflor yellow A,brucine and strychnine in preparation.The determination was performed on Phenomenex Prodigy C18 column with mobile phase consisted of methanol-acetonitrile-0.7％ phosphoric acid soulution(26 ∶ 2 ∶ 72,V/V/V,for hydroxy safflor yellow A),acetonitrile-0.01 mol/L sodium heptanesulfonate mixed with same quantity of 0.02 mol/L potassium dihydrogen phosphate (pH adjusted to 2.8 using 10％ phosphoric acid,21 ∶ 79,V/V,for brucine and strychnine) at the flow rate of 1.0 mL/min.The detection wavelengths were 403 nm (for hydroxy safflor yellow A) and 260 nm (for brucine and strychnine).The column temperature was 25 ℃C,and the injection volume was 10 μL.RESULTS:TLC spots of Chebulae Fructus and Aucklandiae Radix were clear and well-separated without interference from negative control.The linear range was 6.29-62.94 μg/mL for hydroxy safflor yellow A(r=0.999 3),1.83-18.30 μg/mL for brucine(r=0.999 4) and 2.11-21.11 μg/mL for strychnine (r=0.999 6).RSDs of precision,stability and reproducibility tests were lower than 2.0％.The recoveries were 101.66％-104.91％(RSD=1.14％,n=6),99.58％-104.55％ (RSD=1.75％,n=6) and 101.22％-104.04％ (RSD=0.99％,n=6),respectively.CONCLUSIONS:Improved standard can be better used for quality control of Qiwei maqianzi pills.

Study on Stability of Mixture Reference Solution of Strychni Alkaloids / 广州中医药大学学报

Objective Brucine and strychnine monomer reference substance as extremely toxic substance had potential threat during transportation and utilization. In this study we investigated the homogeneity, stability and assignment accuracy of the mixture reference solution of strychnine and brucine, so as to provide reference for the quality control of extremely toxic chemical reference substances for Chinese medicine. Methods Following the assay in Chinese Pharmacopoeia volume I (2015), we prepared the mixture reference solution of brucine and strychnine, and investigated the solvents and the concentration of mixutre reference solution. The stability test lasted for 12 months. F-test was used for heterogeneity assay. Three researchers were involved for collaboration. Results Methanol and chloroform solution were selected as the solvents for the stability test. Results showed the difference was not statistically significant among various mixture solutions. The results of value assignment were 0.14 mg/mL for strychnine (sR = 0.5％)and 0.10 mg/mL for brucine (sR = 1.0％). The stability of mixture solution were better under the conditions of methanol solution at 4 ℃ or -20 ℃. Conclusion The results provide a possible way to develop the mixture solution in place of the monomer reference, and the mixture reference solution is expected for the quality control in the slices of Semen Strychni and its compound preparations.

Equilibrium solubilities, oil-water partition coefficients and in vitro skin permeation features of two constituents in total alkaloids from Strychni Semen / 中成药

AIM To investigate the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of brucine and strychnine in total alkaloids from Strychni Semen.METHODS Saturated dissolution method was applied to determining the equilibrium solubilities of two constituents in ethanol (10％,20％,30％,60％,90％,anhydrous ethanol),trichloromethane,n-octanol and surfactants (0.5％ tween,0.5％ sodium deoxycholate,0.5％ oleic acid).Shake-flask method was adopted in detecting their oil-water partition coefficients in PBS (pH 2.5,4.0,5.0,5.8,6.8,7.0,7.4,9.0).Modified Franz diffusion cell method was used for evaluating their in vitro skin permeation features in PBS,20％ ethanol and anhydrous ethanol.RESULTS Both brucine and strychnine showed the highest equilibrium solubilities in trichloromethane and the lowest equilibrium solubilities in surfactants.The equilibrium solubility of strychnine was higher than that of brucine in ethanol (＞ 20％) or PBS (pH ＜ 8.0),which reached the highest in 60％ ethanol and pH 2.5 PBS,respectively.The similar oil-water partition coefficients of two constituents,proportional to pH value,reached the highest at pH9.0.And they exhibited the highest accumulated transdermal absorptivities in anhydrous ethanol and pH 9.0 PBS,respectively.CONCLUSION Solvent type has obvious effects on the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of both brucine and strychnine.This study can provide a reference for the bioavailability improvement of transdermal drug delivery and development of related preparations.

Equilibrium solubilities, oil-water partition coefficients and in vitro skin permeation features of two constituents in total alkaloids from Strychni Semen / 中成药

AIM To investigate the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of brucine and strychnine in total alkaloids from Strychni Semen.METHODS Saturated dissolution method was applied to determining the equilibrium solubilities of two constituents in ethanol (10％,20％,30％,60％,90％,anhydrous ethanol),trichloromethane,n-octanol and surfactants (0.5％ tween,0.5％ sodium deoxycholate,0.5％ oleic acid).Shake-flask method was adopted in detecting their oil-water partition coefficients in PBS (pH 2.5,4.0,5.0,5.8,6.8,7.0,7.4,9.0).Modified Franz diffusion cell method was used for evaluating their in vitro skin permeation features in PBS,20％ ethanol and anhydrous ethanol.RESULTS Both brucine and strychnine showed the highest equilibrium solubilities in trichloromethane and the lowest equilibrium solubilities in surfactants.The equilibrium solubility of strychnine was higher than that of brucine in ethanol (＞ 20％) or PBS (pH ＜ 8.0),which reached the highest in 60％ ethanol and pH 2.5 PBS,respectively.The similar oil-water partition coefficients of two constituents,proportional to pH value,reached the highest at pH9.0.And they exhibited the highest accumulated transdermal absorptivities in anhydrous ethanol and pH 9.0 PBS,respectively.CONCLUSION Solvent type has obvious effects on the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of both brucine and strychnine.This study can provide a reference for the bioavailability improvement of transdermal drug delivery and development of related preparations.

Determination of Strychnine and Brucine in Strychnos Nux-vomica Linn by SPME-HPLC / 中国药师

Objective:To establish a SPME-HPLC method for the determination of strychnine and brucine in Stryehnos nux-vomiea Linn. Methods:A novel capillary microtube monolithic column coupled with HPLC was prepared for the selective solid-phase microextraction of strychnine and brucine in Stryehnos nux-vomiea Linn. A Hypersil ODS column(150 mm × 4. 6 mm, 5 μm)was used and the mobile phase was acetonitrile- 0. 01 mol·L -1 sodium heptanesulfonate mixed with the same quantity of 0. 02 mol · L -1 potassium dihydrogen phosphate(adjusting pH to 2. 8 with 10% phosphoric acid)(21 ∶79). The detection wavelength was 260 nm,the sample size was 20 μl,and the column temperature was 25℃ . Results:The linear range of strychnine was 1. 2-90. 0μg·ml -1(r = 0. 999 8)and that of brucine was 1. 0-75. 0μg·ml -1(r = 0. 999 6). The average recovery was 100. 05%(RSD = 0. 58% ,n = 6)for strychnine and 99. 98%(RSD = 0. 27% ,n = 6)for brucine. Conclusion:The method is accurate and highly efficient,which can be used for the determination of strychnine and brucine in Stryehnos nux-vomiea Linn.

Research progress on pharmacokinetics of Strychnos nux-vomica and its preparation / 中草药

From the angle of dosage form and administration mode to start, the author reviewed the pharmacokinetics of Strychnos nux-vomica and its dosage forms in recent years. The absolute bioavailability of brucine by ig administration is 33.0%-47.8%, and that by injection is about 75%; With brucine as index, strychnos alkaloid by ig administration has the highest blood drug concentration, followed by brucine and nux vomica powder being the lowest; After injecting the brucine or strychnos alkaloid with liposome as a carrier, the brucine bioavailability was improved greatly; In addition, external preparation can reduce the content of brucine and strychnine in the body, which is beneficial to reduce the toxicity; Oral compound preparation extends the action time of brucine and strychnine in vivo, with reducing the peak concentration. However, the pharmacokinetic study on S. nux-vomica and its dosage forms is relatively weak and needs further exploration.

Simultaneous determination of seven components in Pingxiao Tables by UPLC-Q-TOF-MS / 中草药

Objective: To develop an UPLC-Q-TOF-MS method for the determination of seven components (naringin, hesperidin, strychnine, brucine, agrimol B, wogonin, and protocatechuic acid) in Pingxiao Tablets. Methods: The analysis was performed on a Waters Acquity BEH C18 column (100 mm×2.1 mm, 1.7 μm) with the mixture of acetonitrile-water-formic acid as mobile phase, and the flow rate was 0.45 mL/min; MS scanning mode: negativion; Sample volume: 2.0 μL. Results: The linear relationship between the concentration and peak areas of the seven compounds were all linear (r>0.9996). The average recoveries (n=6) were between 99%-101%. Conclusion: This method is simple, accurate, and reliable to determine the seven contents in Pingxiao Tablets for the quality control.

Research Method on Content Determination of Strychnine and Brucine in Rat Plasma / 世界科学技术-中医药现代化

This study was aimed to establish an effective method for the simultaneous content determination of strychnine and brucine in rat plasma.The Wistar rat plasma samples were processed by liquid-liquid extraction and separated on a UPLC BEH C18 column.The mobile phase was acetonitrile - acid water (17?83).The acid water was 0.02 mol·L-1.The potassium dihydrogen phosphate and 0.014 8 mol·L-1 sodium heptane sulfonate was mixed with equal amount.The 10% phosphonic acid was used to adjust the system to the pH of 2.8.The detection wavelength was set at 260 nm.The results showed that foreign materials in the Wistar rat plasma did not interfere with the content determination of samples.The calibration curve of strychnine was in good linearity within the range of 0.067 84-3.392 00μg·mL-1.The calibration curve of brucine was in good linearity with the range of 0.052 48-2.624 00μg·mL-1.The intra-and inter-day precisions were less than 10%.The mean extraction recoveries were more than 85%.The stability results met the requirements for biopharmaceutical analysis.It was concluded that the UPLC detection method was sensitive and precise,which can be used in the pharmacokinetics study of strychnine and brucine in Tong-Mai(TM) pill.

Rigidez muscular en el servicio de urgencias. A propósito de un caso / Muscular rigidity in the emergency room. A case report

El espectro de manifestaciones neurológicas en el paciente intoxicado es amplio, entre estas tenemos los trastornos del movimiento y dentro de los mismos se encuentran la rigidez el temblor, distonia aguda, diquinesias, mioclonias, corea, etc. Sabiendo que el hallazgo de éstos obedece a diferentes etiologías, dentro de las cuales están medicamentos, toxinas, trastornos metabólicos, infecciones y lesiones estructurales cerebrales, es importante tener un enfoque diagnóstico apropiado desde urgencias. A continuación revisaremos el caso de una paciente con rigidez muscular quien consultó a un servicio de urgencias. La importancia de este caso radica en que hasta la fecha no se encuentran casos reportados en la literatura donde se evidencien simultáneamente dos causas de alteraciones del movimiento como el síndrome de Isaac's y la intoxicación por estricnina.

The spectrum of neurological manifestations in the poisoned patient is wide. The different manifestations include movement disorders and within the same stiffness are tremor, acute dystonia, tardive dyskinesia, myoclonus, chorea, etc. These finding may be a consequence of different etiologies among which are drugs, toxins, metabolic disorders, infections, and structural brain lesions, it is important to have a proper diagnosis from the emergency approach. We review the case of a patient with muscular rigidity who consulted an emergency room. The importance of this case is that where simultaneously two causes of movement disorders as Isaac's syndrome and strychnine poisoning are evident are up to date.