Electromyographic and laboratory findings in acute Solanum torvum poisoning.

CONTEXT: Solanum torvum berries, known as susumber or turkey berries, are prepared as part of traditional Jamaican dishes usually served with cod and rice. Poisoning is rare. Although toxic compounds have never been definitively isolated, previous reports suggest toxicity results from inhibition of acetylcholinesterases. We present a case of susumber berry poisoning with detailed electromyographic studies and laboratory analysis. CASE DETAILS: A 54-year-old woman presented to the Emergency Department (ED) complaining of vision, speech, and gait changes; emesis; and diffuse myalgias following consumption of susumber berries. The physical examination demonstrated an intact, lucid mental status, miosis, opsoclonus, severe dysarthria, dysmetria, mild extremity tenderness and weakness, and inability to ambulate. Her symptom constellation was interpreted as a stroke. DISCUSSION: Electromyography demonstrated a pattern of early full recruitment as well as myotonia during the period of acute toxicity. Additionally, solanaceous compounds, in particular solasonine and solanidine, were identified in leftover berries and the patient's serum. Store-bought commercial berries and subsequent serum samples were free of such toxic compounds. EMG studies, together with a laboratory analysis of berries or serum can assist in the differential diagnosis of stroke, and provide both a prognostic screening and confirmation of suspected glycoside toxicity.

An UPLC-MS/MS method for determination of solasonine in rat plasma and its application of a pharmacokinetic and bioavailability study.

Solasonine, a known glycoalkaloid, is a potential anti-cancer agent. In this work, a simple, sensitive and fast ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of solasonine in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an ACQUITY HSS T3 (100×2.1mm, 1.8µm) column with a gradient mobile phase consisting of 0.1% formic acid and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The validated method had an excellent linearity in the range of 0.1-500ng/mL (R(2)>0.994) with a low limit of detection (0.1ng/mL) and lower limit of quantification (0.5ng/mL). The extraction recovery was in the range of 92.4-94.9% for solasonine and 91.9% for dendrobine (internal standard, IS). The intra- and inter-day precision was below 9.8% and accuracy was from 86.0% to 94.3%. No notable matrix effect and astaticism was observed for solasonine. The method has been successfully applied to a pharmacokinetic and bioavailability study of solasonine in rats for the first time, which provides the basis for the further development and application of solasonine.

Simultaneous determination of atropine, scopolamine, and anisodamine from Hyoscyamus niger L. in rat plasma by high-performance liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetics study.

In order to investigate the pharmacokinetics of tropane alkaloids in Hyoscyamus niger L., a sensitive and specific high-performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of atropine, scopolamine, and anisodamine in rat plasma is developed and fully validated, using homatropine as an internal standard. The separation of the four compounds was carried out on a BDS Hypersil C18 column using a mobile phase consisting of acetonitrile and water (containing 10 mmol ammonium acetate). Calibration curves were linear from 0.2 to 40 ng/mL for atropine, scopolamine, and from 0.08 to 20 ng/mL for anisodamine. The precision of three analytes was <5.89% and the accuracy was between -1.04 to 2.94%. This method is successfully applied to rat pharmacokinetics analysis of the three tropane alkaloids after oral administration of H. niger extract. The maximum concentration of these three tropane alkaloids was reached within 15 min, and the maximum concentrations were 31.36 ± 7.35 ng/mL for atropine, 49.94 ± 2.67 ng/mL for scopolamine, and 2.83 ± 1.49 ng/mL for anisodamine. The pharmacokinetic parameters revealed areas under the curve of 22.76 ± 5.80, 16.80 ± 3.08, and 4.31 ± 1.21 ng/h mL and mean residence times of 2.08 ± 0.55, 1.19 ± 0.45, and 3.28 ± 0.78 h for atropine, scopolamine, and anisodamine, respectively.

Development and validation a liquid chromatography mass spectrometry for determination of solasodine in rat plasma and its application to a pharmacokinetic study.

Solasodine is a poisonous alkaloid chemical compound that occurs in plants of the Solanaceae family. A simple and selective liquid chromatography mass spectrometry method for determination of solasodine in rat plasma was developed and validated over the range of 3-1,000 ng/mL. Chromatographic separation was achieved on a C18 (2.1 mm×50 mm, 3.5 µm) column with acetonitrile-0.1% formic acid in water as mobile phase with gradient elution. The flow rate was set at 0.4 mL/min. After addition of midazolam as internal standard (IS), liquid-liquid extraction by ethyl acetate was used as sample preparation. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification with target ions m/z 414 for solasodine and m/z 326 for IS. Mean recoveries of solasodine in rat plasma were in the range of 87.6-94.1%. Matrix effects for solasodine were between 94.9% and 102.3%. Coefficient of variation of intra-day and inter-day precision were both <13%. The accuracy of the method ranged from 94.4% to 105.3%. The method was successfully applied to a pharmacokinetic study of solasodine after oral administration of 20mg/kg in rats.

Development and validation of a rapid and sensitive assay for the determination of anisodamine in 50 µL of beagle dog plasma by LC-MS/MS.

A simple, rapid, high-throughput, and highly sensitive LC-MS/MS was developed to determine anisodamine in a small volume (50 µL) of beagle dog plasma using atropine sulfate as the internal standard. The analyte and internal standard were isolated from 50 µL plasma samples after a one-step protein precipitation using Sirocco 96-well protein precipitation filtration plates. The separation was accomplished on a Hanbon Hedera CN column (100 × 4.6 mm, 5 µm) and the run time was 4 min. A Micromass Quatro Ultima mass spectrometer equipped with an ESI source was operated in the multiple reaction monitoring mode with the precursor-to-product ion transitions m/z 306.0→140.0 (anisodamine) and 290.0→123.9 (atropine) used for quantitation. The method was sensitive with a low LOQ of 0.05 ng/mL, and good linearity in the range 0.05-50 ng/mL for anisodamine (r(2) ≥ 0.995). All the validation data, such as accuracy, intra- and interrun precision, were within the required limits. The method was successfully applied to the pharmacokinetic study of anisodamine hydrochloride injection in beagle dogs.

Application of high performance capillary electrophoresis on toxic alkaloids analysis.

We employed CE to identify mixtures of the toxic alkaloids lappaconitine, bullatine A, atropine sulfate, atropine methobromide, scopolamine hydrobromide, anisodamine hydrobromide, brucine, strychnine, quinine sulfate, and chloroquine in human blood and urine, using procaine hydrochloride as an internal standard. The separation employed a fused-silica capillary of 75 microm id x 60 cm length (effective length: 50.2 cm) and a buffer containing 100 mM phosphate and 5% ACN (pH 4.0). The sample was injected in a pressure mode and the separation was performed at a voltage of 16 kV and a temperature of 25 degrees C. The compounds were detected by UV absorbance at wavelengths of 195 and 235 nm. All the ten alkaloids were separated within 16 min. The method was validated with regard to precision (RSD), accuracy, sensitivity, linear range, LOD, and LOQ. In blood and urine samples, the detection limits were 5-40 ng/mL and linear calibration curves were obtained over the range of 0.02-10 microg/mL. The precision of intra- and interday measurements was less than 15%. Electrophoretic peaks could be identified either by the relative migration time or by their UV spectrum.

[Studies on the determination of plasma level and pharmacokinetic parameters of anisodamine by micellar liquid chromatography].

Anisodamine is a tropane alkaloid isolated from the plant Anisodus tanguticus (Maxim) Pasch. It is an anticholine drug widely used in clinics. Micellar liquid chromatography is a new type of HPLC developed in the 1980's. Direct plasma injection technique is the application of micellar HPLC in bioanalyses. In this paper, a micellar HPLC method, which employs n-propanol as modifier, SDS as surfactant, atropine sulphate as internal standard, has been developed. By direct injection, this method was successfully applied to the measurement of plasma level of anisodamine. Application of this method to the study of anisodamine pharmacokinetics was investigated in human volunteers following a single intramuscular injection. The separation was performed in a Shim-pack CLC-CN column (150 mm x 6 mm ID, 5 microns) with a mobile phase of n-propanol-water (15:85) with 45 mmol/L SDS and total ion strength 70 mmol/L by adding phosphate, and detected at 205 nm. The standard curve was linear over the concentration range of 15-750 ng plasma level (r = 0.9972). The measurable lowest concentration was 10 ng/ml plasma (S/N = 3:1). The study of anisodamine pharmacokinetic in man was also described.

Determination of potato glycoalkaloids and their aglycone in blood serum by high-performance liquid chromatography. Application to pharmacokinetic studies in humans.

The development of a high-performance liquid chromatography (HPLC) method for the separation and quantification of potato glycoalkaloids and their aglycone solanidine in blood serum is reported. High selectivity was obtained by using solid-phase extraction followed by off-line dual-column HPLC. Injections were made via a sample enrichment column to achieve maximum sensitivity in the assay. The potato alkaloids in the HPLC effluents were detected by ultraviolet absorption at 200 nm. The detection limits were estimated to be 0.3 ng/ml of serum for each of the alkaloids. The method was used to study the pharmacokinetics of potato glycoalkaloids in humans. alpha-Solanine and alpha-chaconine were detected in all blood serum samples collected from seven volunteers 1-25 h after a meal of potatoes. Solanidine was detected in some samples, but there were no traces of the mono- or diglycosides. The average apparent biological half-lives for alpha-solanine and alpha-chaconine were 11 and 19 h, respectively.

Potato steroidal alkaloids and neural tube defects: serum concentrations fail to demonstrate a causal relation.

Spoiled potatoes and, in particular, steroidal alkaloids have been proposed as an aetiological factor in the pathogenesis of neural tube defect (NTD). The present study involves the measurement of potato (solanum) steroidal alkaloid concentrations in serum by radioimmunoassay. Serum solanidine and total potato alkaloid concentrations were measured in two groups of women: one group pregnant with a fetus, subsequently shown to be affected by a NTD, the other with a healthy fetus. Serum alkaloid concentrations were, contrary to expectations, lower in the NTD group. They lend no weight therefore to the theory that potato alkaloids are responsible for NTD, but are consistent with the opinion that some water-soluble vitamins lessen the risk.

Measurement of potato steroidal alkaloids in human serum and saliva by radioimmunoassay.

Radioimmunoassay methods are described for measuring potentially toxic potato glycoalkaloids and the aglycone solanidine in human serum and saliva. Solanidine and total alkaloid concentrations in serum and saliva during the summer are given for a group of subjects from the UK and a group from Sweden. Serum concentrations ranged from 3.2 to greater than 125 nmol/l for total alkaloid and 2.5 to 92.5 nmol/l for solanidine and were comparable in the two populations. Salivary total alkaloid concentrations were only about 10% of serum values. Salivary solanidine concentrations did not exceed 20% of the serum levels. Good correlation was found between serum and salivary alkaloid concentrations (r = 0.734, for solanidine; r = 0.892 for total alkaloid). Serum and salivary alkaloid concentrations were significantly raised in a group of Swedish subjects eating potatoes containing unusually high concentrations of alkaloids when compared with those in a group of subjects eating their normal diets.

Solanidine is present in sera of healthy individuals and in amounts dependent on their dietary potato consumption.

Solanidine, a steroidal alkaloid, and its glycosides have been reported to have caused poisoning in man and animals. These alkaloids are normally present in small amounts in potatoes. Measurement of solanidine in body fluid would be expected to establish the real incidence of acute toxicity and help to resolve the question of any chronic toxicity including teratogenicity. We report the detection of solanidine in the serum of 57 normal healthy volunteer subjects in whom it measured 4.0-56.3 nmol/l (1.6-22.5 ng/ml) before the midday meal. There was a significant correlation between serum solanidine concentration and normal dietary intake of potato by the individual concerned. When two subjects abstained from potato and its products serum solanidine fell markedly and became minimal after the second week onwards.

Determination of solanidine in human plasma by radioimmunoassay.

A radioimmunoassay for solanidine, the major hydrolysis product of potato glycoalkaloids, has been established and validated for application to human plasma. All 34 samples of human plasma tested contained solanidine, with a mean of 1.27 +/- 0.97 ng/ml (3.18 +/- 2.43 nmol/litre).

Kinetics and retention of solanidine in man.

1. When [3H]solanidine was administered to normal human subjects by i.v. injection, the tritium concentration in the erythrocytes was 2-5 times greater than in the plasma. Three phases in the clearance of tritium from the plasma were identified having half-times of 2-5 min, 120-300 min and 70-105 h. 2. Rates of excretion of 3H in urine and faeces were low: 24 h after administration, 1-4% of the dose of 3H had been excreted in urine and 1-3% in faeces. During the following week the combined rates of excretion were about 2% a day. 3. Solanidine has been detected in human post-mortem liver and its identity confirmed by mass spectroscopy. 4. These data show that solanidine is absorbed from the diet and stored in the body for prolonged periods of time. We suggest that at times of increased metabolic stress (pregnancy, starvation, debilitating illness), stored solanidine might be mobilized from innocuous loci with deleterious effects.