Capillary electrophoresis with electrochemiluminescence detection for the simultaneous determination of cisatracurium besylate and its degradation products in pharmaceutical preparations.

Capillary electrophoresis with electrochemiluminescence detection for the simultaneous analysis of cisatracurium besylate and its degradation products (laudanosine, quaternary monoacrylate) in pharmaceutical preparation was developed and fully validated. The significant parameters that influence capillary electrophoresis separation and electrochemiluminescence detection were optimized. The total analysis time of the analytes was 15 min. The linearities of the method were 0.1∼40.0 µg/mL for cisatracurium besylate and 0.04∼8.00 µg/mL for laudanosine, with correlation coefficients (r) of 0.999 and 0.998, respectively. The detection limits (S/N = 3) were 83.0 ng/mL for cisatracurium besylate and 32.0 ng/mL for laudanosine. The intraday relative standard deviations of the analytes were <3.0%, and the interday relative standard deviations were <8.0%. The developed method was cost-effective, sensitive, fast, and resource-saving, which was suitable for the ingredient analysis in pharmaceutical preparation.

Impact of temperature exposure on stability of drugs in a real-world out-of-hospital setting.

STUDY OBJECTIVE: The aim of this study is to determine the content of 5 important emergency medical services (EMS) drugs after being stored at the recommended refrigerated temperature, room temperature, or in an emergency physician transport vehicle operating under real-world working conditions. METHODS: Adrenaline hydrochloride, cisatracurium besylate, lorazepam, methylergonovine maleate, and succinylcholine chloride were stored for 1 year under the 3 conditions. For each storage condition, samples of the drugs were taken after 1, 2, 3, and 4 weeks and after 2, 4, 6, 8, 10, and 12 months. For adrenaline hydrochloride, however, the samples were taken after 1, 2, 4, 6, 8, 10, and 12 months. The samples were analyzed with a validated high-performance liquid chromatography assay. A drug was considered stable if its content was above 90%. RESULTS: Adrenaline hydrochloride and methylergonovine maleate remained stable for 1 year at room temperature and in the emergency physician transport vehicle. At room temperature and in the emergency physician transport vehicle, lorazepam became unstable within 4 weeks. Succinylcholine chloride was stable for 2 months at room temperature and for 1 month in the emergency physician transport vehicle. Cisatracurium besylate became unstable within 4 months at room temperature. However, it remained stable for 4 months in the emergency physician transport vehicle. CONCLUSION: When stored at room temperature or in the emergency physician transport vehicle, lorazepam became unstable within weeks, whereas succinylcholine chloride and cisatracurium besylate became unstable within months. Adrenaline hydrochloride and methylergonovine maleate remained stable for several months, even under room temperature and emergency physician transport vehicle conditions. Thus, real-world EMS working conditions pose challenges for maintaining optimal efficacy of these important EMS drugs.

HPLC determination of cisatracurium besylate and propofol mixtures with LC-MS identification of degradation products.

A stability-indicating HPLC method was developed to simultaneously determine cisatracurium besylate and propofol in mixtures. The effects of organic modifier, ionic strength and the pH of the mobile phase on resolution and retention were investigated. A baseline separation was achieved on an octadecylsilane column with an isocratic mobile phase of acetonitrile-ammonium formate (pH 5.2; 0.3 M) (50:50, v/v). Cisatracurium and propofol were confirmed by both retention time and mass-to-charge ratio using LC-MS. The degradation products of cistracurium were identified by ESI positive-ion detection as Hofmann elimination and ester hydrolysis products of cisatracurium. There were no propofol degradation products observed. The quantitation of the two drugs was accomplished using UV detection at 280 nm. This method showed linearity for cisatracurium besylate and propofol in the 9-128 and 37-592 micrograms ml-1 ranges, respectively. Accuracy and precision were in the 0.4-1.4 and 0.4-2.9% ranges respectively, for both analytes.

Identification of laudanosine, an atracurium metabolite, following a fatal drug-related shooting.

In a case involving a fatal shooting, toxicology tests on blood and urine demonstrated the presence of cocaine metabolites and a large amount of an unidentified compound. This compound was subsequently identified by mass spectral, gas chromatographic, and thin layer chromatographic tests as laudanosine, a metabolite of the skeletal muscle relaxant atracurium which was administered during emergency surgery. Identification was confirmed by comparison with commercially available standards. Because of the difficulty associated with isolating and chromatographing highly water-soluble compounds, recognition of this artifact is a useful tool in identifying these cases.

Determination of atracurium, cisatracurium and mivacurium with their impurities in pharmaceutical preparations by liquid chromatography with charged aerosol detection.

The Corona CAD (charged aerosol detection) is a new type of detector introduced for LC applications that has recently become widely applied in pharmaceutical analysis. The Corona CAD measures a physical property of analyte and responds to almost all non-volatile species, independently of their nature and spectral or physicochemical properties. The LC method with charged aerosol detection was developed for the determination of three isomers of atracurium, cisatracurium and also three isomers of mivacurium with their impurities. The limit of quantitation for laudanosine was 1 microg ml(-1). The elaborate method for the analysis of those active substances and laudanosine proved to be fast, precise, accurate and sensitive. All other impurities were identified using time-of-flight mass spectrometry with electrospray ionization.

Simultaneous determination of atracurium and its metabolite laudanosine in post-mortem fluids by liquid chromatography/multiple-stage mass spectrometry on an ion trap.

A method was developed to accurately quantify atracurium (a non-depolarizing skeletal muscle relaxant) and its metabolite laudanosine in post-mortem specimens. Analytes were isolated from blood and tissues by liquid/liquid extraction after adding vecuronium as an internal standard. Chromatographic separation was accomplished by gradient elution in a Synergy Max RP 150 x 2.1 mm column. Positive ion electrospray ionization and mass spectrometric analyses were carried out in an ion trap mass spectrometer under collision-induced dissociation conditions. The method proved selective and sensitive, and was validated in post-mortem blood, heart, lung and liver in the range of 1-2000 ng/mL (blood) and 5-5000 ng/g (tissues); the limits of quantification obtained were 1 ng/mL in blood and 5 ng/g in tissues.

The stability of atracurium in clinical practice.

Atracurium has an unusual intrinsic Hofmann elimination which is increased by an alkaline environment and increased temperature. Normally the relaxant is stored at pH 3.3 and kept at a temperature of 4 degrees C. However, it is convenient to have a reasonable quantity available within the operating theatre. This study examined the rate of degradation of atracurium in the operating theatre environment of 20 degrees C. Atracurium within one month of its expiry date was placed in the drawer for anaesthetic drugs in each of three operating theatres. At the end of each month, further drug was added to the stock. At the end of the study, atracurium which had been stored continuously at 4 degrees C, was at 102.9% of nominal strength, having started with 113.5% at manufacture. Atracurium which had been at room temperature for one, two and three months respectively retained 99%, 95% and 92% strength respectively. These results show that even three months' exposure to room temperature does not cause enough deterioration to be clinically significant.

Simultaneous determination of atracurium besylate and its major decomposition products and related impurities by reversed-phase high-performance liquid chromatography.

The separation and determination of atracurium besylate and its major decomposition products and related impurities using octadecylsilica columns and acetonitrile-phosphate buffer mobile phases were studied. The influence of the acetonitrile and buffer concentrations and the pH of the mobile phase on the retention was investigated. The results indicated that hydrophobic and silanophilic interactions contribute to the retention of the compounds investigated.

High-performance liquid chromatography as a diagnostic tool in prolonged neuromuscular blockade.

We report the use of high-performance liquid chromatography (HPLC) to identify the cause of prolonged neuromuscular blockade in a child who had received 2 mg.kg-1 of succinylcholine. Upon analysis by HPLC the syringe was found to contain succinylcholine (10 mg.ml-1) and also atracurium (5 mg.ml-1), so that a diagnosis was established. In situations where medication errors are suspected, we recommend saving syringe contents for analysis for confirmation of the agent.

Atracurio mas alcuronio en anestesia / Atracurio and alcuronio in anesthesia

Con el presente trabajo se busca demostrar los beneficios del ejemplo alternado en un mismo paciente de dos relajantes musculares no despolarizantes, en este caso atracurio y alcuronio, obteniendose condiciones optimas mas o menos rapidas de intubacion endo-traqueal, adecuada relajacion quirurgica, sin la necesidad de revertir a estos relajantes al finalizar el acto quirurgico. Disminuyendo de esta forma la dosis total de ambos relajantes, probabilidad de depresion respiratoria por relajacion residual post anestesica.