[Propofol: use, toxicology and assay features]. / Propofol: primenenie, toksikologicheskaya kharakteristika i osobennosti opredeleniya.

The study objective is to review the literature on the use, pharmacological properties, toxicology, and assay methods for intravenous anesthetic propofol. The scope and forms of propofol use, its pharmacokinetics, biotransformation features, which occurs more than 90% in the liver, and side effects associated with propofol use for anesthesia, are addressed. Propofol infusion syndrome (also known as PrIS) and deaths from propofol overdose due to medical errors, abuse, suicide attempts, and homicide are reported. Propofol identification and assay methods based on high-performance liquid chromatography (HPLC), gas chromatography with mass spectrometry (GC-MS), and liquid chromatography (LC) are described. The features of the methods performance are outlined; biological materials (the study objects) are listed: mainly blood and plasma, as well as urine, bile, hair, etc. The relevance of a comprehensive forensic chemical study of propofol is indicated, though there are few forensic studies of propofol.

Online monitoring of end-tidal propofol in balanced anesthesia by anisole assisted positive photoionization ion mobility spectrometer.

Online measuring end-tidal propofol concentration during balanced anesthesia is important for anesthetists to learn the patient's anesthesia depth as exhaled propofol concentration is well related to blood propofol concentration. In previous work, exhaled propofol was detected using acetone assisted negative photoionization ion mobility spectrometer, however, the existence of high concentration sevoflurane interfered the response of propofol. In this work, an anisole assisted photoionization ion mobility spectrometer operated in positive mode was developed to sensitively and selectively measure the end-tidal propofol by eliminating the interferences of exhaled humidity and sevoflurane during balanced anesthesia. Anisole molecular ion is stable enough not to go under proton transfer reaction with water presents in the exhaled breath. Hence, the exhaled humidity related peaks were eliminated and only one propofol product ion peak (K0 = 1.50 cm2 V-1 s-1) was observed. The relative standard deviation (RSD) ranging from 0.64%-0.91% showed good repeatability and the quantitative range was 0.2-40 ppbv with a response time of 4 s. Finally, the performance of the proposed method was demonstrated by monitoring end-tidal propofol of balanced anesthetized patients during gastric cancer surgery.

Evaluating Propofol Concentration in Blood From Exhaled Gas Using a Breathing-Related Partition Coefficient.

BACKGROUND: The anesthetic side effects of propofol still occur in clinical practice because no reliable monitoring techniques are available. In this regard, continuous monitoring of propofol in breath is a promising method, yet it remains infeasible because there is large variation in the blood/exhaled gas partial pressure ratio (RBE) in humans. Further evaluations of the influences of breathing-related factors on RBE would mitigate this variation. METHODS: Correlations were analyzed between breathing-related factors (tidal volume [TV], breath frequency [BF], and minute ventilation [VM]) and RBE in 46 patients. Furthermore, a subset of 10 patients underwent pulmonary function tests (PFTs), and the parameters of the PFTs were then compared with the RBE. We employed a 1-phase exponential decay model to characterize the influence of VM on RBE. We also proposed a modified RBE (RBEM) that was not affected by the different breathing patterns of the patients. The blood concentration of propofol was predicted from breath monitoring using RBEM and RBE. RESULTS: We found a significant negative correlation (R = -0.572; P < .001) between VM and RBE (N = 46). No significant correlation was shown between PFTs and RBE in the subset (N = 10). RBEM demonstrated a standard Gaussian distribution (mean, 1.000; standard deviation [SD], 0.308). Moreover, the predicted propofol concentrations based on breath monitoring matched well with the measured blood concentrations. The 90% prediction band was limited to within ±1 µg·mL. CONCLUSIONS: The prediction of propofol concentration in blood was more accurate using RBEM than when using RBE and could provide reference information for anesthesiologists. Moreover, the present study provided a general approach for assessing the influence of relevant physiological factors and will inform noninvasive and accurate breath assessment of volatile drugs or metabolites in blood.

[Climate footprint of halogenated inhalation anesthetics]. / Klimateffekterna från anestesin kan minska.

This study estimated the climate footprint of halogenated inhalation anesthetics in Sweden and estimated effects of a decreased use of these compounds. We collected data on sales of desflurane, sevoflurane and isoflurane in Sweden during 2017 and calculated the mass of CO2 equivalents (CO2e) using Global Warming Potential data over 100 years for the compounds. Inhalation anesthetics contributed by 5000 tons of CO2e which corresponds to 0.005 percent of the Swedish climate footprint. By replacing desflurane with sevoflurane the footprint can be reduced by 73 percent. By replacing sevoflurane with intravenous propofol the climate effect can be reduced further by at least 2 orders of magnitude.

Quality control and stability of ketamine, remifentanil, and sufentanil syringes in a pediatric operating theater.

BACKGROUND: Transforming a drug from its commercial form into a ready-to-use drug is common practice, especially in pediatrics. However, the risk of compounding error is real and data on drug stability in practice are not always available. AIMS: The aim of this study was to assess, in real conditions, both the error rate and stability of three drugs: ketamine, remifentanil, and sufentanil. METHODS: A new rapid and easy-to-use high-performance liquid chromatography method with a diode array detector has been developed and validated to quantify these drugs and detect their degradation products. Over a 1-month period, 151 syringes were collected in the postanesthesia care unit. Seventy-three were stock solution syringes containing a 10-fold dilution of commercial drugs and 78 were serial dilution syringes made from successive dilutions of stock solutions. A comparison between real and expected concentrations as well as the detection of possible degradation products was carried out on these samples. RESULTS: All stock solution syringes had good chemical stability throughout the working day. A 4-µg/mL remifentanil serial dilution syringe, however, had to be discarded as a degradation peak was detected. Overall, 15.3% (95% CI, 9.5-21.1%) of syringes had a drug concentration outside the ±10% acceptability range, that is, 11.0% (95% CI, 3.7-18.2%) and 19.5% (95% CI, 10.6%-28.4%) of stock and diluted syringes respectively, with drug amounts ranging from -25.3% to 22.0%. The highest error rates were observed with sufentanil syringes: 20% and 28% for stock solution and serial dilution, respectively. CONCLUSION: The study shows that stock solution syringes prepared in advance are chemically stable throughout the day, unlike certain serial dilution syringes, indicating that the latter should be prepared just before administration to ensure chemical stability. Our results show that the error rate for serial dilution syringes is twice that of stock solution. Different safety measures are under discussion and have to be further studied.

Evaluation of the stability and stratification of propofol and ketamine mixtures for pediatric anesthesia.

BACKGROUND: The combination of propofol and ketamine is commonly used for total intravenous anesthesia. These drugs can be delivered in different syringes or in the same syringe. We hypothesized that the drugs might separate and different concentrations of each drug could be found in different parts of the syringe during the procedure period when they were mixed in 1 syringe. METHODS: Twelve 60-mL polypropylene syringes were prepared by mixing propofol and ketamine as 4 groups on the basis of propofol/ketamine mixture ratios (5:1 and 6.7:1) and propofol solution concentrations. Syringes were placed upright in the vertical position into a rack and kept at room temperature (21.5-22.5°C), in daylight conditions and were not moved for 360 minutes. Samples of the mixture were taken from both the top and the bottom of the syringe. The first 1 mL of the samples was discarded, the following second 1 mL of the samples was filtered using 0.2-µm polytetrafluoroethylene filters and measured twice (n = 6). Samples were taken at the following time intervals: T0, T10, T30, T60, T90, T120, T180, T240, T300, and T360 min. Syringes were checked visually for any color change and separation lines between the drugs. RESULTS: There were no significant differences between the propofol and ketamine concentrations of the top and bottom samples in all 4 groups. In addition, there were no statistically significant changes of propofol and ketamine concentrations of samples over 360 minutes in any of the 4 groups. No visual changes were observed during 6 hours' observation. CONCLUSION: The results of our measurements demonstrated that mixtures of propofol (1% and 2%) and ketamine at 5:1 and 6.7:1 ratios could be used in terms of mixture homogeneity and stability in a polypropylene syringe during a 6-hour period at room temperature.

An Analysis of Substandard Propofol Detected in Use in Zambian Anesthesia.

BACKGROUND: In early 2015, clinicians throughout Zambia noted a range of unpredictable adverse events after the administration of propofol, including urticaria, bronchospasm, profound hypotension, and most predictably an inadequate depth of anesthesia. Suspecting that the propofol itself may have been substandard, samples were procured and sent for testing. METHODS: Three vials from 2 different batches were analyzed using gas chromatography-mass spectrometry methods at the John L. Holmes Mass Spectrometry Facility. RESULTS: Laboratory gas chromatography-mass spectrometry analysis determined that, although all vials contained propofol, its concentration differed between samples and in all cases was well below the stated quantity. Two vials from 1 batch contained only 44% ± 11% and 54% ± 12% of the stated quantity, whereas the third vial from a second batch contained only 57% ± 9%. The analysis found that there were no hexane-soluble impurities in the samples. CONCLUSIONS: None of the analyzed vials contained the stated amount of propofol; however, our analysis did not detect additional contaminants that would explain the adverse events reported by clinicians. Our results confirm the presence of substandard propofol in Zambia; however, anecdotal accounts of substandard anesthetic medicines in other countries abound and warrant further investigation to provide estimates of the prevalence and scope of this global problem.

Adherence of volatile propofol to various types of plastic tubing.

Propofol is an intravenous anesthetic. Currently, it is not possible to routinely measure blood concentration of the drug in real time. However, multi-capillary column ion-mobility spectrometry of exhaled gas can estimate blood propofol concentration. Unfortunately, adhesion of volatile propofol on plastic materials complicates measurements. Therefore, it is necessary to consider the extent to which volatile propofol adheres to various plastics used in sampling tubing. Perfluoralkoxy (PFA), polytetrafluorethylene (PTFE), polyurethane (PUR), silicone, and Tygon tubing were investigated in an experimental setting using a calibration gas generator (HovaCAL). Propofol gas was measured for one hour at 26 °C, 50 °C, and 90 °C tubing temperature. Test tubing segments were then flushed with N2 to quantify desorption. PUR and Tygon sample tubing absorbed all volatile propofol. The silicone tubing reached the maximum propofol concentration after 119 min which was 29 min after propofol gas exposure stopped. The use of PFA or PTFE tubing produced comparable and reasonably accurate propofol measurements. The desaturation time for the PFA was 10 min shorter at 26 °C than for PTFE. PFA tubing thus seems most suitable for measurement of volatile propofol, with PTFE as an alternative.

Propofol Breath Monitoring as a Potential Tool to Improve the Prediction of Intraoperative Plasma Concentrations.

INTRODUCTION: Monitoring of drug concentrations in breathing gas is routinely being used to individualize drug dosing for the inhalation anesthetics. For intravenous anesthetics however, no decisive evidence in favor of breath concentration monitoring has been presented up until now. At the same time, questions remain with respect to the performance of currently used plasma pharmacokinetic models implemented in target-controlled infusion systems. In this study, we investigate whether breath monitoring of propofol could improve the predictive performance of currently applied, target-controlled infusion models. METHODS: Based on data from a healthy volunteer study, we developed an addition to the current state-of-the-art pharmacokinetic model for propofol, to accommodate breath concentration measurements. The potential of using this pharmacokinetic (PK) model in a Bayesian forecasting setting was studied using a simulation study. Finally, by introducing bispectral index monitor (BIS) measurements and the accompanying BIS models into our PK model, we investigated the relationship between BIS and predicted breath concentrations. RESULTS AND DISCUSSION: We show that the current state-of-the-art pharmacokinetic model is easily extended to reliably describe propofol kinetics in exhaled breath. Furthermore, we show that the predictive performance of the a priori model is improved by Bayesian adaptation based on the measured breath concentrations, thereby allowing further treatment individualization and a more stringent control on the targeted plasma concentrations during general anesthesia. Finally, we demonstrated concordance between currently advocated BIS models, relying on predicted effect-site concentrations, and our new approach in which BIS measurements are derived from predicted breath concentrations.

Time-resolved dynamic dilution introduction for ion mobility spectrometry and its application in end-tidal propofol monitoring.

Based on the adsorption of analytes in the sampling loop, a time-resolved dynamic dilution introduction method was developed for negative ion mobility spectrometry to continuously monitor end-tidal propofol without other sample pre-separation. The dynamic dilution characteristics of propofol and moisture in the Teflon sample loop (4 mm o.d. and 2.4 mm i.d., 150 cm length) were both theoretically and experimentally investigated. The prominent absorption differences between propofol and moisture on the inwall of the sample loop allowed their concentrations to be time-resolved during the injection process, realizing sensitive measurement of end-tidal propofol with a response time of 2 s. At the optimized carrier gas flow rate of 700 mL min(-1), the linear response range for propofol was achieved to be 0.2 to 20 ppbv with a limit of detection (LOD) of 65 pptv. Finally, this method was performed on a patient undergoing mastectomy surgery to continuously monitor the end-tidal propofol with an interval of five respirations and the result nicely demonstrated its fast response to the propofol changes.

Gas chromatograph-surface acoustic wave for quick real-time assessment of blood/exhaled gas ratio of propofol in humans.

BACKGROUND: Although pilot studies have reported that exhaled propofol concentrations can reflect intraoperative plasma propofol concentrations in an individual, the blood/exhaled partial pressure ratio RBE varies between patients, and the relevant factors have not yet been clearly addressed. No efficient method has been reported for the quick evaluation of RBE and its association with inter-individual variables. METHODS: We proposed a novel method that uses a surface acoustic wave (SAW) sensor combined with a fast gas chromatograph (GC) to simultaneously detect propofol concentrations in blood and exhaled gas in 28 patients who were receiving propofol i.v. A two-compartment pharmacokinetic (PK) model was established to simulate propofol concentrations in exhaled gas and blood after a bolus injection. Simulated propofol concentrations for exhaled gas and blood were used in a linear regression model to evaluate RBE. RESULTS: The fast GC-SAW system showed reliability and efficiency for simultaneous quantitative determination of propofol in blood (correlation coefficient R(2)=0.994, P<0.01) and exhaled gas (R(2)=0.991, P<0.01). The evaluation of RBE takes <50 min for a patient. The distribution of RBE in 28 patients showed inter-individual differences in RBE (median 1.27; inter-quartile range 1.07-1.59). CONCLUSIONS: Fast GC-SAW, which analyses samples in seconds, can perform both rapid monitoring of exhaled propofol concentrations and fast analysis of blood propofol concentrations. The proposed method allows early determination of the coefficient RBE in individuals. Further studies are required to quantify the distribution of RBE in a larger cohort and assess the effect of other potential factors. CLINICAL TRIAL REGISTRATION: ChiCTR-ONC-13003291.

Propofol modulates the lipid phase transition and localizes near the headgroup of membranes.

The compound 2,6-diisopropylphenol (Propofol, PRF) is widely used for inducing general anesthesia, but the mechanism of PRF action remains relatively poorly understood at the molecular level. This work examines the possibility that a potential mode of action of PRF is to modulate the lipid order in target membranes. The effect on monolayers and bilayers of dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) was probed using Langmuir monolayer isotherms, differential scanning calorimetry (DSC), isothermal titration calorimetry (ITC) and molecular dynamics (MD) simulations. Increasing amounts of PRF in a DPPC monolayer causes a decrease in isothermal compressibility modulus at the phase transition. A partition constant for PRF in DPPC liposomes on the order of K≈1500 M(-1) was found, and the partitioning was found to be enthalpy-driven above the melting temperature (Tm). A decrease in Tm with PRF content was found whereas the bilayer melting enthalpy ΔHm remains almost constant. The last finding indicates that PRF incorporates into the membrane at a depth near the phosphatidylcholine headgroup, in agreement with our MD-simulations. The simulations also reveal that PRF partitions into the membrane on a timescale of 0.5 µs and has a cholesterol-like ordering effect on DPPC in the fluid phase. The vertical location of the PRF binding site in a bacterial ligand-gated ion channel coincides with the location found in our MD-simulations. Our results suggest that multiple physicochemical mechanisms may determine anesthetic potency of PRF, including effects on proteins that are mediated through the bilayer.

Determination of breath isoprene allows the identification of the expiratory fraction of the propofol breath signal during real-time propofol breath monitoring.

Real-time measurement of propofol in the breath may be used for routine clinical monitoring. However, this requires unequivocal identification of the expiratory phase of the respiratory propofol signal as only expiratory propofol reflects propofol blood concentrations. Determination of CO2 breath concentrations is the current gold standard for the identification of expiratory gas but usually requires additional equipment. Human breath also contains isoprene, a volatile organic compound with low inspiratory breath concentration and an expiratory concentration plateau. We investigated whether breath isoprene could be used similarly to CO2 to identify the expiratory fraction of the propofol breath signal. We investigated real-time breath data obtained from 40 study subjects during routine anesthesia. Propofol, isoprene, and CO2 breath concentrations were determined by a combined ion molecule reaction/electron impact mass spectrometry system. The expiratory propofol signal was identified according to breath CO2 and isoprene concentrations and presented as median of intervals of 30 s duration. Bland-Altman analysis was applied to detect differences (bias) in the expiratory propofol signal extracted by the two identification methods. We investigated propofol signals in a total of 3,590 observation intervals of 30 s duration in the 40 study subjects. In 51.4 % of the intervals (1,844/3,590) both methods extracted the same results for expiratory propofol signal. Overall bias between the two data extraction methods was -0.12 ppb. The lower and the upper limits of the 95 % CI were -0.69 and 0.45 ppb. Determination of isoprene breath concentrations allows the identification of the expiratory propofol signal during real-time breath monitoring.

On-line measurement of propofol using membrane inlet ion mobility spectrometer.

The concentration of propofol in patient's exhaled air is an indicator of the anesthetic depth. In the present study, a membrane inlet ion mobility spectrometer (MI-IMS) was built for the on-line measurement of propofol. Compared with the direct sample introduction, the membrane inlet could eliminate the interference of moisture and improve the selectivity of propofol. Effects of membrane temperature and carrier gas flow rate on the sensitivity and response time have been investigated experimentally and theoretically. Under the optimized experimental conditions of membrane temperature 100 °C and carrier gas flow rate 200 mL min(-1), the calculated limit of detection (LOD) for propofol was 1 ppbv, and the calibration curve was linear in the range of 10-83 ppbv with a correlation coefficient (R(2)) of 0.993. Finally, the propofol concentration in an anaesthetized mouse exhaled air was monitored continuously to demonstrate the capability of MI-IMS in the on-line measurement of propofol in real samples.

Toward feedback-controlled anesthesia: voltammetric measurement of propofol (2,6-diisopropylphenol) in serum-like electrolyte solutions.

Propofol is a widely used, potent intravenous anesthetic for ambulatory anesthesia and long-term sedation. The target steady state concentration of propofol in blood is 0.25-10 µg/mL (1-60 µM). Although propofol can be oxidized electrochemically, monitoring its concentration in biological matrixes is very challenging due to (i) low therapeutic concentration, (ii) high concentrations of easily oxidizable interfering compounds in the sample, and (iii) fouling of the working electrode. In this work we report the performance characteristics of an organic film coated glassy carbon (GC) electrode for continuous monitoring of propofol. The organic film (a plasticized PVC membrane) improved the detection limit and the selectivity of the voltammetric sensor due to the large difference in hydrophobicity between the analyte (propofol) and interfering compounds of the sample, e.g., ascorbic acid (AA) or p-acetamidophenol (APAP). Furthermore, the membrane coating prevented electrode fouling and served as a protective barrier against electrode passivation by proteins. Studies revealed that sensitivity and selectivity of the voltammetric method is greatly influenced by the composition of the PVC membrane. The detection limit of the membrane-coated sensor for propofol in PBS is reported as 0.03 ± 0.01 µM. In serum-like electrolyte solutions containing physiologically relevant levels of albumin (5%) and 3 mM AA and 1 mM APAP as interfering agents, the detection limit was 0.5 ± 0.4 µM. Both values are below the target concentrations used clinically during anesthesia or sedation.

Life cycle greenhouse gas emissions of anesthetic drugs.

BACKGROUND: Anesthesiologists must consider the entire life cycle of drugs in order to include environmental impacts into clinical decisions. In the present study we used life cycle assessment to examine the climate change impacts of 5 anesthetic drugs: sevoflurane, desflurane, isoflurane, nitrous oxide, and propofol. METHODS: A full cradle-to-grave approach was used, encompassing resource extraction, drug manufacturing, transport to health care facilities, drug delivery to the patient, and disposal or emission to the environment. At each stage of the life cycle, energy, material inputs, and emissions were considered, as well as use-specific impacts of each drug. The 4 inhalation anesthetics are greenhouse gases (GHGs), and so life cycle GHG emissions include waste anesthetic gases vented to the atmosphere and emissions (largely carbon dioxide) that arise from other life cycle stages. RESULTS: Desflurane accounts for the largest life cycle GHG impact among the anesthetic drugs considered here: 15 times that of isoflurane and 20 times that of sevoflurane on a per MAC-hour basis when administered in an O(2)/air admixture. GHG emissions increase significantly for all drugs when administered in an N(2)O/O(2) admixture. For all of the inhalation anesthetics, GHG impacts are dominated by uncontrolled emissions of waste anesthetic gases. GHG impacts of propofol are comparatively quite small, nearly 4 orders of magnitude lower than those of desflurane or nitrous oxide. Unlike the inhaled drugs, the GHG impacts of propofol primarily stem from the electricity required for the syringe pump and not from drug production or direct release to the environment. DISCUSSION: Our results reiterate previous published data on the GHG effects of these inhaled drugs, while providing a life cycle context. There are several practical environmental impact mitigation strategies. Desflurane and nitrous oxide should be restricted to cases where they may reduce morbidity and mortality over alternative drugs. Clinicians should avoid unnecessarily high fresh gas flow rates for all inhaled drugs. There are waste anesthetic gas capturing systems, and even in advance of reprocessed gas applications, strong consideration should be given to their use. From our results it appears likely that techniques other than inhalation anesthetics, such as total i.v. anesthesia, neuraxial, or peripheral nerve blocks, would be least harmful to the environment.

Drug detection in breath: effects of pulmonary blood flow and cardiac output on propofol exhalation.

Breath analysis could offer a non-invasive means of intravenous drug monitoring if robust correlations between drug concentrations in breath and blood can be established. In this study, propofol blood and breath concentrations were determined in an animal model under varying physiological conditions. Propofol concentrations in breath were determined by means of two independently calibrated analytical methods: continuous, real-time proton transfer reaction mass spectrometry (PTR-MS) and discontinuous solid-phase micro-extraction coupled with gas chromatography mass spectrometry (SPME-GC-MS). Blood concentrations were determined by means of SPME-GC-MS. Effects of changes in pulmonary blood flow resulting in a decreased cardiac output (CO) and effects of dobutamine administration resulting in an increased CO on propofol breath concentrations and on the correlation between propofol blood and breath concentrations were investigated in seven acutely instrumented pigs. Discontinuous propofol determination in breath by means of alveolar sampling and SPME-GC-MS showed good agreement (R(2)=0.959) with continuous alveolar real-time measurement by means of PTR-MS. In all investigated animals, increasing cardiac output led to a deterioration of the relationship between breath and blood propofol concentrations (R(2)=0.783 for gas chromatography-mass spectrometry and R(2)=0.795 for PTR-MS). Decreasing pulmonary blood flow and cardiac output through banding of the pulmonary artery did not significantly affect the relationship between propofol breath and blood concentrations (R(2)>0.90). Estimation of propofol blood concentrations from exhaled alveolar concentrations seems possible by means of different analytical methods even when cardiac output is decreased. Increases in cardiac output preclude prediction of blood propofol concentration from exhaled concentrations.

Time course of ethanol and propofol exhalation after bolus injection using ion molecule reaction-mass spectrometry.

The transit of ethanol from blood to breath gas is well characterised. It is used for intraoperative monitoring and in forensic investigations. A further substance, which can be measured in breath gas, is the phenol propofol. After a simultaneous bolus injection, the signals (time course and amplitude) of ethanol and propofol in breath gas were detected by ion molecule reaction-mass spectrometry (IMR-MS) and compared. After approval by the regional authorities, eight pigs were endotracheally intubated after a propofol-free induction with etomidate. Boluses of ethanol (16 µg/kg) and propofol (4 or 2 mg/kg) were infused alone and in combination. For both substances, breath gas concentrations were continuously measured by IMR-MS; the delay time, time to peak and amplitude were determined and compared using non-parametric statistic tests. IMR-MS allows a simultaneous continuous measurement of both substances in breath gas. Ethanol appeared (median delay time, 12 vs 29.5 s) and reached its peak concentration (median time to peak, 45.5 vs 112 s) significantly earlier than propofol. Time courses of ethanol and propofol in breath gas can be simultaneously described with IMR-MS. Differing pharmacological and physicochemical properties of the two substances can explain the earlier appearance and time to peak of ethanol in breath gas compared with propofol.

A simple and sensitive method for the determination of propofol in human solid tissues by gas chromatography-mass spectrometry.

Propofol is a widely used intravenous agent for induction and maintenance of anesthesia and for sedation in intensive care patients, but it is also associated with abuse and dependency. A simple and sensitive method for the determination of propofol in human whole blood, brain, liver, and adipose tissue by gas chromatography-mass spectrometry using selected-ion monitoring mode is described. Propofol was extracted from 0.2-mL or 0.2-g sample size by a single-step basic extraction procedure using 100 microL heptane with thymol (50 ng) as an internal standard. The calibration curves of the specimens were linear in the concentration range of 10-5000 ng/mL or ng/g, and the limit of detection was 2.5 ng/mL in blood, 5.0 ng/g in brain and liver, and 10 ng/g in adipose tissue. Absolute recovery of propofol was determined in three samples and averaged over 95% for blood and brain, 66% for liver, and 51% for adipose tissue. Within-day and between-day precision was measured in five samples each at 50 and 500 ng/mL or ng/g in all specimens and was determined to be less than 10%. The developed propofol method was applied to a forensic autopsy case where a suspected propofol misinjection occurred eight days prior to death, and the tissue analysis was vital to the case.