Aerodynamic Thermal Breakup Droplet Ionization in Mass Spectrometric Drug Analysis.

Aerodynamic thermal breakup droplet ionization (ATBDI) in mass spectrometric drug analysis is considered. Cocaine, heroin, and the main alkaloids of opium (morphine, codeine, papaverine) were chosen as the test compounds. The principles of ATBDI ionization are discussed. The dependences of the intensities of the peaks of the target compounds on temperature during ATBDI ionization are also considered. In some cases, a comparison of ATBDI ionization with electrospray ionization (ESI) was performed. In addition, a comparison of methods is demonstrated by the analysis of confiscated opium that was provided by the local police department. Five major alkaloids are found in opium: morphine, codeine, thebaine, papaverine, and narcotine.

Detection of opium alkaloids in a Cypriot base-ring juglet.

A method has been developed for extracting poppy alkaloids from oily matrices, specifically lipid residues associated with archaeological ceramics. The protocol has been applied to fresh and artificially aged poppyseed oil and to residue from a Late Bronze Age Cypriot juglet in the collections of the British Museum. The juglet is of a type that has been linked with ancient trade in opium due to its poppy-head shape and wide distribution; it is a rare example of an intact vessel with contents sealed inside. Bulk analysis of the residue by GC-EI-MS and pyGC-EI-MS indicated a degraded plant oil and possible presence of papaverine. Analysis of the alkaloid extracts by HPLC-ESI-MS using both triple quadrupole and FTICR mass spectrometers detected the five primary opium alkaloids in fresh poppyseed oil and papaverine in most of the aged samples. Papaverine and thebaine were detected in the juglet residue, providing the first rigorous chemical evidence to support a link between this vessel type and opium, or at least poppies. The association of opium with oil raises new questions about the ancient purpose of the commodities within these vessels, and the low levels (ng g-1) of opiates detected in this unusually well-preserved residue shed doubt on the scope for their detection in more fragmentary ceramic remains (potsherds). Papaverine was found to exhibit challenging carryover behaviour in all the analytical methods used in this study. The phenomenon has not been reported before and should be considered in future analyses of this analyte in all application areas.

Evaluation of hydrophilic interaction liquid chromatography stationary phases for analysis of opium alkaloids.

The separation of a mixture containing five major opium alkaloids, namely morphine, codeine, thebaine, noscapine and papaverine has been investigated in hydrophilic interaction liquid chromatography (HILIC) mode using five different stationary phases: bare silica, zwitterion, aminopropyl, diol and cyanopropyl. In order to propose the appropriate column for separation and purification, retention behaviors of the five natural opioids have been studied on mentioned HILIC stationary phases. The mechanism of separation in diverse HILIC media, based on the formation of water-rich layer on surface of the HILIC stationary phases and the physicochemical properties of opium alkaloids, such as pKa (acidic pK) and the octanol-water distribution coefficient (log Do/w) are discussed. Chromatographic responses including modified limit of detection LODm, signal to noise ratio (S/N)m, and defined modified RSm have considered for suggestion of the suitable column for quantitative/qualitative and preparative purposes. According to the obtained results, diol stationary phase is best suited for analytical chromatography, whereas bare silica and zwitterionic stationary phases are appropriate for preparative applications.

[Simultaneous determination of 5 kinds of alkaloids in Kechuanning tablets by SPE-UPLC under different UV-vis wavelength].

The paper is to establish a method for simultaneous determination of 5 kinds of alkaloids in ephedra and poppy which are in Kechuanning tablets. Solid-phase extraction (SPE) was adopted in pretreatment, and a UPLC method with 2 different wavelengths had been developed: 210 nm for the detection of morphine, codeine phosphate, ephedrine hydrochloride and pseudoephedrine hydrochloride, and 251 nm for papaverine hydrochloride. The column used was Acquity UPLC BEH C18 (100 mm x 2.1 mm ID, 1.7 microm) with linear gradient elution using acetonitrile and 0.1% phosphoric acid. The flow rate was 0.4 mL.min-1, and the column temperature was 30 degrees C. The linear response range was 0.375 0 - 12.50 microg.mL-1 for morphine, 0.064 32 - 2.144 microg.mL-1 for codeine phosphate, 0.030 06 - 1.002 microg.mL-1 for papaverine hydrochloride, 1.126 - 37.52 microg.mL-1 for ephedrine hydrochloride, 0.287 8 - 9.592 microg.mL-1 for pseudoephedrine hydrochloride (r = 0.999 7). The average recoveries of these compounds were 99.26%, 100.6%, 95.29%, 100.1% and 97.48%, respectively. This is a more reasonable and credible method of quality control for Kechuanning tablets.

[Absorption of papaverine, laudanosine and cepharanthine across human intestine by using human Caco-2 cells monolayers model].

Absorption of papaverine (PAP), laudanosine (LAU) and cepharanthine (CEP) as some chemical constituents of traditional Chinese medicines in human intestine were studied. By using Caco-2 (the human colonic adenocarcinoma cell lines) cell monolayers as an intestinal epithelial cell model, the permeability of PAP, LAU and CEP were studied from apical side (AP side) to basolateral side (BL side) or from BL side to AP side. The three alkaloids were measured by reversed-phase high-performance liquid chromatography coupled with UV detector. Transport parameters and apparent permeability coefficients (Papp) were then calculated and compared with those of propranolol as a control substance of high permeability and atenolol as a control substance of poor permeability. The Papp values of PAP, LAU and CEP were (3.524+/-0.223) x 10(-5), (2.821+/-0.050) x 10(-5) and (6.524+/-0.052) x 10(-5) cm s(-1) from AP side to BL side, and (5.095+/-0.508) x 10(-5), (2.646+/-0.146) x 10(-5) and (5.495+/-0.036) x 10(-5) cm s(-1) from BL side to AP side, respectively. Their Papp values were identical with those of propranolol, which is a transcellular transport marker. On the other hand, the efflux transport of PAP was 1.45 times higher than its influx transport with 0.69 rate of P(app A-->B)/P(app B-->A). But P(app A-->B)/P(app B-->A) values of LAU and CEP were 1.07 and 1.19, respectively, which suggested that the efflux transport have not been involved in their absorbed mechanism in Caco-2 cells monolayers. There is a good correlation between the Papp value and apparent distribution coefficient (Log D) at pH 7.35 for the three alkaloids. PAP, LAU and CEP can be absorbed across intestinal epithelial cells, and they are completely absorbed compounds. PAP may have been involved in efflux mechanism in Caco-2 cells monolayers model from the basolateral-to-apical direction. The O/W (oil/water) partition coefficient plays key role in their transmembrane permeation.

Extraction and determination of papaverin in pericarpium papaveris using aqueous two-phase system of poly(ethylene glycol)-(NH4)2SO4 coupled with high-performance liquid chromatography.

Based on aqueous two-phase system (ATPS) of poly(ethylene glycol) (PEG)-(NH4)2SO4, a simple pretreatment approach was developed for the extraction and determination of papaverin in pericarpium papaveris. The influence factors on phase behavior of the ATPS and partition behavior of papaverin was investigated, and partition mechanism based on the hydrophobic interaction between PEG and analyte molecules was proposed. Under the optimal conditions, the extraction efficiencies for papaverin were 93-96%, and the recoveries of the added standard were 97-106% with relative standard deviations of 1.8-2.5%. Combined with a high-performance liquid chromatography (HPLC) method, this extraction technique has been successfully applied to the determination of papaverin in pericarpium papaveris with the detection limit of 2 ng mL(-1) and the linear range of 0.10-10 microg mL(-1). Compared with the conventional liquid-liquid extraction or solid-phase extraction, this method was more environmentally benign, more cost effective and much simpler due to the direct injection of the upper phase into HPLC system.

[Determination of papaverine in Qiangli Pipalu by HPLC].

OBJECTIVE: To establish a method for the determination of the papaverine content in Qiangli Pibalu by HPLC. METHOD: A C18 column with a solvent system of acetonitrile-0.02 mol x L(-1) sodium dihydrogen phosphate (0.2% triethylamine, phosphoric acid, at pH 3) (25:75) and UV detection 240 nm were used. The flow rate was 1.0 mL x min(-1). The column temperature was maintained at 40 degrees C. RESULT: There was a good linear relationship between the absorption value and the concentration in the range of 0.020 2-0.100 5 microg for papaverine. The average recovery rates were 99.1% (RSD 2.3%). CONCLUSION: The method is simple, accurate and can be used to determine the contents in Qiangli Pibalu.

[Determination of papaverine in seeds of Papaver somniferum L. and soup of chafing dish by high performance liquid chromatography-fluorescence detection].

A method of reversed-phase high performance liquid chromatography coupled with fluorescence detection was developed for the separation and determination of papaverine in seeds of Papaver somniferum L. and soup of chafing dish. The liquid chromatographic experiment was carried out under the following conditions: the detector was a fluorescence with excitation wavelength at 285 nm and emission wavelength at 355 nm. An RP-C18 column (250 mm x 4.6 mm i.d., 5 microm) was used. The mobile phase was a mixture of methanol and 0.02 mol/L ammonium acetate (70: 30, v/v). The flow rate was 0.8 mL/min. A linear range was obtained from 0.1 ng to 0.1 microg with a good correlation. The lowest detection limit was 0.02 ng. The average recovery of seeds for Papaver somniferum L. was 99.0% - 100.8%. The method is rapid, accurate, sensitive and suitable for the separation and determination of papaverine in foods.

[Influence of fertilizers on yield and yield components of opium from Papaver somniferum Linn].

The effect of fertilizer on the yield and yield components of opium from Papaver somniferum L.cv.Ikkanshu were investigated from 1993 to 1995. The weight of opium per one capsule was tendency to increase in the order of peat moss > pulverized charcoal > compound fertilizer, but the differences among the results were not significant. Furthermore, no difference in the capsule weight per 100 m2 and the yields of opium and alkaloids per 100 m2 were detected. The significant difference was only observed when the data were compared among the weights and yields of different years. The difference among the yield of opium was mainly due to the weight of opium per one capsule. The weight of opium per one capsule showed a high correlation with capsule husk weight. The alkaloids contents in opium obtained with a different fertilizer application showed no difference. Morphine content at the first lancing was about 11%, and the value decreased with the order of lancing. On the contrary, the codeine and the thebaine content did not change during lancing and the value were 6-7% and 3%, respectively. The papaverine and the noscapine content decreased in the order of lancing.

Gas chromatographic/mass spectrometric detection of narcotine, papaverine, and thebaine in seeds of Papaver somniferum.

In addition to codeine and morphine, three more compounds: narcotine (noscapine), papaverine, and thebaine were found in Indian and Netherlands poppy seeds (Papaver somniferum L). The compounds were detected by a GC/MS technique and the identities were confirmed by comparing retention times and ion ratios with the known references. The concentrations of codeine, morphine, thebaine, papaverine, and narcotine were 44, 167, 41, 67, and 230 micrograms/g in Indian poppy seeds, and were 1.8, 39, 1.0, 0.17, 0.84 micrograms/g in Netherlands poppy seeds, respectively. Because these compounds may be urinary products after poppy seed consumption, the lowest detectable concentrations of codeine, morphine, thebaine, papaverine, and narcotine in urine are of interest and were found to be 4, 4, 5, 0.4, and 4 ng/ml, respectively. The detection of urinary narcotine, papaverine, or thebaine may be utilized to differentiate poppy seed consumption from illicit codeine, morphine, or heroin use.

Differentiation and comparison of raw, prepared and dross opium.

Comparative studies involving colour tests, thin-layer chromatography (TLC) and gas-liquid chromatography (GLC) were made on raw, prepared and dross opium with a view to establishing means for their differentiation. Analysis of a large number of samples found in south-east Asia showed the typical patterns and results to be quite distinctive in the qualitative and quantitative aspects. The relative proportions of the major alkaloids in the two chromatographic systems were used to advantage in the comparison. Prepared opium was found to have a characteristic yellow fluorescent spot on the TLC plate when viewed under long-wavelength ultraviolet light. No positive marker was found for dross opium, its unusual features being the relatively high morphine and codeine content and the absence of narcotine, meconic acid and especially thebaine. Most of the prepared opium samples were found to have been made from a mixture of raw and dross opium. The modified hallucinogen reagent of Maunder was found to be a suitable alternative chromogenic spray in the TLC analysis.

High pressure liquid chromatographic determination of the five major alkaloids in Papaver somniferum L. and thebaine in Papaver bracteatum Lindl. capsular tissue.

A high pressure liquid chromatographic isocratic procedure is described for determining and quantitating the 5 major alkaloids narcotine, papaverine, thebaine, codeine, and morphine in Papaver somniferum L. and thebaine in Papaver bracteatum Lindl. Other papaveraceous alkaloids, including salutaridine, oripavine, laudanosine, isothebaine, cryptopine, alpinigenine, narceine, protopine, and gnoscopine, were also quantitated. The values for morphine, codeine, and thebaine in P. somniferum were in agreement within 5--9% with values obtained by the United Nations Narcotics Laboratory by other methods. In contrast to previously reported procedures, the advantage of this method is that no precolumn or other purification other than solvent extraction of the capsular tissue is necessary. Isocratic chromatography alone on a single column resolved the 5 major alkaloids.

Rapid semi-quantitative spot test for determination of thebaine and differentiation of Papaver bracteatum from P. orientale and P. pseudo-orientale.

The alkaloids, orientalidine, oripavine, thebaine, narceine, narceine, codeine, papaverine, isothebaine, alpenigenine and morphine react with a solution of sulfuric acid containing molybdate to give specific colors. Using the acid solution permitted the differentiation of Papaver bracteatum latex from P. orientale latex and P. pseudo-orientale latex.

Ligand-exchange chromatography of alkaloids.

Alkaloids are separated by liquid chromatography on resins having functional carboxyl groups combined with copper (II) ions. The eluent is aqueous alcohol containing ammonia. Some resins retain alkaloids much better than others. Alkaloids studied included morphine, codeine, strychnine, atropine, papaverine, narcotine, cocaine, quinine, cinchonine and methadone.