Simultaneous Determination Of Morphine Research Articles

Engagement of computerized and electrochemical methods to develop a novel and intelligent electronic device for detection of heroin abuse

In this work, a novel biosensing platform was fabricated based on modification of a rotating glassy carbon electrode (GCE) with chitosan-ionic liquid (Ch-IL) composite film, electrochemical synthesis of gold palladium platinum trimetallic three metallic alloy nanoparticles (AuPtPd NPs) onto its surface, and electrosynthesis of dual templates molecularly imprinted polymers (MIPs) where morphine (MO) and codeine (COD) used as template molecules. The AuPtPd NPs were synthesized under different electrochemical conditions, and surfaces of electrodes were investigated by digital image processing, and the best electrode was chosen. Effects of experimental variables on response of the biosensor to MO and COD were optimized by a central composite design (CCD), and under optimized conditions (concentration of the phosphate buffered solution (PBS): 0.09 M, pH of the PBS: 3.21–3.2, time of immersion: 204.8–205 s, and rotation rate: 2993.51–3000 rpm) the biosensor responses to MO and COD were individually calibrated (1–20 pM for MO and 0.5–12 pM for COD), three-way calibrated by PARASIAS, PARAFAC2, and MCR-ALS, and validated in the presence of ascorbic acid and uric acid as uncalibrated interference. Finally, performance of the biosensor in simultaneous determination of MO and COD in the presence of ascorbic acid and uric acid as uncalibrated interference in human serum samples were verified and compared with the results of HPLC-UV as the reference method which guaranteed it as a reliable method.

Machine learning-enhanced drug testing for simultaneous morphine and methadone detection in urinary biofluids

The simultaneous identification of drugs has considerable difficulties due to the intricate interplay of analytes and the interference present in biological matrices. In this study, we introduce an innovative electrochemical sensor that overcomes these hurdles, enabling the precise and simultaneous determination of morphine (MOR), methadone (MET), and uric acid (UA) in urine samples. The sensor harnesses the strategically adapted carbon nanotubes (CNT) modified with graphitic carbon nitride (g-C3N4) nanosheets to ensure exceptional precision and sensitivity for the targeted analytes. Through systematic optimization of pivotal parameters, we attained accurate and quantitative measurements of the analytes within intricate matrices employing the fast Fourier transform (FFT) voltammetry technique. The sensor’s performance was validated using 17 training and 12 test solutions, employing the widely acclaimed machine learning method, partial least squares (PLS), for predictive modeling. The root mean square error of cross-validation (RMSECV) values for morphine, methadone, and uric acid were significantly low, measuring 0.1827 µM, 0.1951 µM, and 0.1584 µM, respectively, with corresponding root mean square error of prediction (RMSEP) values of 0.1925 µM, 0.2035 µM, and 0.1659 µM. These results showcased the robust resiliency and reliability of our predictive model. Our sensor’s efficacy in real urine samples was demonstrated by the narrow range of relative standard deviation (RSD) values, ranging from 3.71 to 5.26%, and recovery percentages from 96 to 106%. This performance underscores the potential of the sensor for practical and clinical applications, offering precise measurements even in complex and variable biological matrices. The successful integration of g-C3N4-CNT nanocomposites and the robust PLS method has driven the evolution of sophisticated electrochemical sensors, initiating a transformative era in drug analysis.

Developing a miniaturized setup for in‐tube simultaneous determination of three alkaloids using electromembrane extraction in combination with ultraviolet spectrophotometry

Herein, electromembrane extraction was combined with ultraviolet spectrophotometry using a customized manifold for preconcentration and simultaneous determination of morphine, codeine, and papaverine in water and human urine samples. Absorption spectra of the extracts were recorded inside the lumen of the hollow fiber using two fiber optics connected to a miniature spectrophotometer. Partial least squares regression was applied to resolve the overlapped spectra of the analytes. Performance of the model was validated by an independent test set. Central composite design was applied to optimize the extraction parameters. The optimized extraction conditions are as follows; supporting liquid membrane: 2-nitrophenyl octyl ether containing 15% v/v bis(2-ethylhexyl) phosphate, applied voltage: 80 V, donor pH: 3.0, acceptor pH: 1.0, extraction time: 20 min. Finally, the optimized extraction method was validated for determination of the mentioned alkaloids in human urine samples. The method showed good linearity (R2 >0.995) for all of the mentioned alkaloids. The limits of detection for morphine, codeine, and papaverine in diluted human urine were found to be 0.6, 1.1, and 0.6ng/mL, respectively with acceptable relative standard deviations. Enrichment factors of 104, 108, and 102 were achieved for morphine, codeine, and papaverine, respectively.

Cobalt Oxide Nanoparticles/Graphene/Ionic Liquid Crystal Modified Carbon Paste Electrochemical Sensor for Ultra-sensitive Determination of a Narcotic Drug.

Purpose: Drug-abuse, namely morphine (MO) affects the metabolism of neurotransmitters such as dopamine (DA). Therefore, it is crucial to devise a sensitive sensing technique to simultaneously determine both compounds in real samples. Methods: The fabrication of the sensor is based on in situ modification of a carbon paste (CP) electrode with cobalt oxide nanoparticles, graphene, and ionic liquid crystal in presence of sodium dodecyl sulfate; CoGILCCP-SDS. The modified sensor is characterized using scanning electron microscopy, electrochemical impedance spectroscopy and voltammetry measurements. Results: Electron transfer kinetics and analytical performance of the proposed sensor were enhanced due to the synergistic role of all the modifiers. The simultaneous determination of MO and DA achieved low detection limits of 0.54 nmol L−1 and 0.25 nmol L−1, respectively. Besides, a carbon-based electrochemical sensor is fabricated for the nano-molar determination of MO in real samples and formulations. The sensor showed fouling resistance and anti-interference ability in presence of other species in human fluids. The real sample analysis of MO was successfully achieved with good recovery results in urine samples and pharmaceutical tablets. Linear dynamic range, sensitivity, detection limit and quantification limit of MO in urine were 5 nmol L−1 to 0.6 μmol L−1, 6.19 μA/μmol L-1, 0.484 nmol L−1 and 1.61 nmol L−1, respectively. Conclusion: This sensor has great ability to be extended for electrochemical applications in assaying of many drugs.

Application of multivariate optimization method in nanomolar simultaneous determination of morphine and codeine in the presence of uric acid using a glassy carbon electrode modified with a hydroxyapatite-Fe3O4 nanoparticle/multiwalled carbon nanotubes composite

The electrochemical oxidation of morphine (MO) and codeine (COD) has been investigated by the application of a novel glassy carbon electrode modified with a hydroxyapatite-Fe3O4 nanoparticles/multiwalled carbon nanotubes composite (HA-FeNPs-MWCNTs/GCE). The modified electrode worked as an efficient sensor for simultaneous determination of MO and COD in the presence of uric acid. Response surface methodology was utilized to optimize the voltammetric response of the modified electrode for the determination of MO and COD. The amount of HA-FeNPs in the modifier matrix (%HA-FeNPs), the solution pH and the accumulation time were chosen as the three important operating factors through the experimental design methodology. The central composite design as a response surface approach was applied for obtaining the optimum conditions leading to maximum oxidation peak currents for MO and COD. The differential pulse voltammetry results showed that the obtained anodic peak currents were linearly proportional to concentration in the range of 0.08–32 µM with a detection limit (S/N = 3.0) of 14 nM for MO and in the range of 0.1–28 µM and with a detection limit of 22 nM for COD. The proposed method was successfully applied to determine these compounds in human urine and blood serum samples.

Simultaneous Determination of Morphine, Codeine, Pentazocine and Propoxyphene in Urine Using HPTLC

Opiate abuse is a major problem worldwide. Simple and cost-effective method with quantification capabilities is need of time especially for developing countries. A procedure for simultaneous determination of morphine, codeine, pentazocine and propoxyphenene in urine by High performance thin layer chromatography (HPTLC) is described. Following enzymatic hydrolysis, urine samples were extracted. Liquid-liquid extraction was carried out with dichloromethane and isopropanol (9: 3) at pH 9. Extracts reconstituted in methanol were analyzed by HPTLC in quantification mode. Limit of quantification (LOQ) was120 μg/ml for morphine and codeine with 20 ml of urine sample. For propoxyphene LOQ was 60 μg/ml and pentazocine 800 μg/ml with 20 ml of urine sample. This study is an attempt to utilize HPTLC for semi-quantification of biological sample. Unavailability of HPTLC inserts forced to take larger urine volume. Software (wincats) inability to save calibration curve resulted in preparation of calibration curve on regular basis.

Combination of electrochemistry with chemometrics to introduce an efficient analytical method for simultaneous quantification of five opium alkaloids in complex matrices

For the first time, an analytical methodology based on differential pulse voltammetry (DPV) at a glassy carbon electrode (GCE) and integration of three efficient strategies including variable selection based on ant colony optimization (ACO), mathematical pre-processing selection by genetic algorithm (GA), and sample selection (SS) through a distance-based procedure to improve partial least squares-1 (PLS-1, ACO-GA-SS-PLS-1) multivariate calibration (MVC) for the simultaneous determination of five opium alkaloids including morphine (MOP), noscapine (NOP), thebaine (TEB), codeine (COD), and papaverine (PAP) was used and validated. The baselines of the DPV signals were modeled as a smooth curve, using P-splines, a combination of B-splines and a discrete roughness penalty. After subtraction of the baseline we got a signal with a two-component probability density. One component was for the peaks and it was approximated by a uniform distribution on the potential axis. The other component was for the observed noise around the baseline. Some sources of bi-linearity deviation for electrochemical data were discussed and analyzed. The lack of bi-linearity was tackled by potential shift correction using correlation optimized warping (COW) algorithm. The MVC model was developed as a quinternary calibration model in a blank human serum sample (drug-free) provided by a healthy volunteer to regard the presence of a strong matrix effect which may be caused by the possible interferents present in the serum, and it was validated and tested with two independent sets of analytes mixtures in the blank and actual human serum samples, respectively. Fortunately, the proposed methodology was successful in simultaneous determination of MOP, NOP, TEB, COD, and PAP in both blank and actual human serum samples and its results were satisfactory comparable to those obtained by applying the reference method based on high performance liquid chromatography-ultraviolet detection (HPLC-UV).

Simultaneous determination of morphine, codeine and 6-acetyl morphine in human urine and blood samples using direct aqueous derivatisation: Validation and application to real cases

Opiates play a relevant role in forensic toxicology and their assay in urine or blood is usually performed for example in workplace drug-testing or toxicological investigation of drug impaired driving. The present work describes two new methods for detecting morphine, codeine and 6-monoacethyl morphine in human urine or blood using a single step derivatisation in aqueous phase. Propyl chloroformate is used as the dramatizing agent followed by liquid-liquid extraction and gas-chromatography-mass spectroscopy to detect the derivatives. The methods have been validated both for hydrolysed and unhydrolysed urine. For hydrolysed urine, the LOD and LOQ were 2.5ng/ml and 8.5ng/ml for codeine, and 5.2ng/ml and 15.1ng/ml for morphine, respectively. For unhydrolysed urine, the LOD and LOQ were 3.0ng/ml and 10.1ng/ml for codeine, 2.7ng/ml and 8.1ng/ml for morphine, 0.8ng/ml and 1.5ng/ml for 6-monoacetyl morphine, respectively. In blood, the LOD and LOQ were 0.44ng/ml and 1.46ng/ml for codeine, 0.29ng/ml and 0.98ng/ml for morphine, 0.15ng/ml and 0.51ng/ml for 6-monoacetyl morphine, respectively. The validated methods have been applied to 50 urine samples and 40 blood samples (both positive and negative) and they can be used in routine analyses.

Simultaneous Determination of Morphine, Morphine Glucuronides (M3G, M6G) and Oxycodone in Human Plasma by High-performance Liquid Chromatography

Morphine and oxycodone are widely used as analgesic drugs for cancer pain. Frequently, morphine and oxycodone are given alternately to avoid adverse drug reactions. Morphine is metabolized primarily into two glucuronide metabolites, morphine-3-glucuronide and morphine-6-glucuronide to be pharmacologically active. Morphine-3-glucuronide and morphine-6-glucuronide have neuroexcitatory action and analgesic activity, respectively. Oxymorphone, a metabolite of oxycodone, has an analgesic effect, however it is so small that it can be neglected when considering oxycodone. The pharmacological effects of these drugs and also their metabolites have been reported in experimental papers, but in humans, the relationships between these plasma concentrations and the clinical effects remain unclear. Also the necessity for simultaneous determination of both drugs has been suggested because opioid rotation is performed clinically. However, to date there is no study which has simultaneously determined these four drugs, and also achieved a high recovery. In this paper, in order to perform a reliable pharmacokinetic study of cancer pain patients receiving morphine and oxycodone, an easy, rapid, sensitive and selective analytical method was proposed and validated.

Simultaneous determination of morphine, oxycodone, morphine-3-glucuronide, and noroxycodone concentrations in rat serum by high performance liquid chromatography–electrospray ionization–tandem mass spectrometry

An assay using high performance liquid chromatography (HPLC)–electrospray ionization–tandem mass spectrometry (ESI–MS–MS) was developed for simultaneously determining concentrations of morphine, oxycodone, morphine-3-glucuronide, and noroxycodone, in 50 μl samples of rat serum. Deuterated (d 3) analogues of each compound were used as internal standards. Samples were treated with acetonitrile to precipitate plasma proteins; acetonitrile was removed from the supernatant by centrifugal evaporation before analysis. Limits of quantitation (ng/ml) and their between-day accuracy and precision (%deviation and %CV) were—morphine, 3.8 (4.3% and 7.6%); morphine-3-glucuronide, 5.0 (4.5% and 2.9%); oxycodone, 4.5 (0.4% and 9.3%); noroxycodone, 5.0 (8.5% and 4.6%).

Simultaneous determination of morphine and its glucuronides in rat hair and rat plasma by reversed-phase liquid chromatography with electrospray ionization mass spectrometry.

The simultaneous determination of morphine and the glucuronide metabolites [morphine-3-beta-D-glucuronide (M3G) and morphine-6-beta-D-glucuronide (M6G)] in rat hair and rat plasma was carried out using reversed-phase high-performance liquid chromatography (HPLC) coupled with electrospray ionization mass spectrometry (ESI-MS). The chromatographic separation of the analytes was achieved using a semi-micro-HPLC column (3 microm particle size; 100 x 2.0 mm id) by gradient elution with 50 mM ammonium acetate and acetonitrile as eluents. After separation, morphine and the glucuronides were determined by selected ion monitoring (SIM) of ESI-MS using the quasi-molecular ions [M + H]+ at m/z = 286 and 462, respectively. The calibration curves were linear between the concentration of the analytes and the deuterium-labelled morphine (M-d3) selected as internal standard. The method was applied for the determination of the incorporation of morphine and the glucuronides into the hair shafts and hair roots of Dark Agouti rats after single intraperitoneal administration of morphine hydrochloride. Plasma concentrations of morphine and glucuronides were simultaneously determined after administration. Morphine and M3G were detected in the hair shafts and the hair roots. The concentrations of M3G in the hair root were lower than those of morphine in all sampling periods. In contrast, M3G concentrations in plasma were relatively higher at each sampling time. Small quantities of M6G were also identified in the plasma up to 4 h after administration. The concentration difference between the hair root and plasma seems to be due to the incorporation ratio of morphine and glucuronide into hair. As M3G was also identified in the hair shaft 1 week after administration, the incorporation of glucuronide metabolites into hair is obvious. This is the first report of the identification of morphine glucuronide in hair samples without the use of acid hydrolysis or enzyme digestion.

Simultaneous determination of morphine and codeine in blood and bile using dual ultraviolet and fluorescence high-performance liquid chromatography.

The separation and identification of morphine and codeine from postmortem blood and bile was accomplished using a liquid-phase extraction method followed by reversed-phase high-performance liquid chromatography with combined UV and fluorescence detection. Identification of morphine and codeine was based on relative retention time matching with calibration standards, together with their fluorescence-to-UV response ratios. Linear calibration curves for morphine and codeine ranged from 0.10 to 3.0 mg/L for blood and 5.0 to 100 mg/L for bile. Morphine concentrations (in autopsy cases), where the intravenous use of heroin or morphine was suspected as the cause of death, were 0.10-0.89 mg/L (mean, 0.29 mg/L) for blood and 3.3-112 mg/L (mean, 38 mg/L) for bile. Codeine concentrations, where therapeutic use or overdosage of codeine occurred, were 0.06-6.4 mg/L (mean, 1.5 mg/L) in blood and 0.22-89 mg/L (mean, 24 mg/L) in bile. This method allowed simultaneous detection of morphine and codeine from blood and bile with little interference from extraneous peaks. The procedure described provides a selective, sensitive, accurate, and reliable method suitable for both clinical and forensic toxicology.

Comparative Study of Different Solid-Phase Extraction Cartridges in the Simultaneous RP-HPLC Analysis of Morphine and Codeine in Biological Fluids

Abstract A comparative study of different Solid-Phase Extraction (SPE) Cartridges for the extraction and purification of morphine and codeine in plasma and urine samples is presented. A rapid and sensitive Reversed-Phase isocratic High-Performance Liquid Chromatographic (RP-HPLC) method has been developed for the simultaneous determination of morphine and codeine in plasma and urine samples, using quinine as internal standard. The drugs were extracted from the sample matrices by using the SPE technique and a series of cartridges from different manufacturers and with different sorbents were tested. The best recover)' from plasma was achieved with Alltech C'8 cartridges and the best recovery from urine with Bakerbond C18 cartridges. The HPLC analysis was performed with an Adsorbosphere HS C18, ODS, 5 pm. 250 × 4.6 mm I. D., column and UV detection at 241 nm and it was completed within approximately 10 min. The mobile phase was a mixture of methanol-acetonitrile 0.1 M ammonium acetate (40 : 25 : 35 v/v) and ...

A Stereospecific Microassay for the Determination of Morphine-6-β-D-Glucuronide and other Active Morphine Metabolites in the Neonatal Guinea Pig

Abstract A stereospecific microassay for the simultaneous determination of morphine and active metabolites morphine-6-β-D-glucuronide, morphine-3-β-D-glucuronide and normorphine using reversed-phase high-performance liquid-chromatography with ultraviolet detection is described. Solid-phase extraction was followed by chromatography on an octadecylsilica column eluted by 16.5% acetonitrile in phosphate buffer, pH 2.1 with sodium dodecyl sulfate as an ion-pairing agent. Using an 80 μl sample size the limits of quantitation were 94 ng/ml for all drugs. Coefficients of variation ranged from 2.0% to 6.3%. The assay is specific and separates the stereoisomers morphine-6-α-D-glucuronide and morphine-6-β-D-glucuronide. This microassay has been applied to samples of guinea pig plasma, following subcutaneous injections of morphine, and to hepatic microsomal enzyme preparations from a pregnant guinea pig. Neonatal guinea pigs produce substantial amounts of morphine-3-glucuronide and morphine-6-glucuronide from morphi...

A Simple, Rapid Method for the Simultaneous Determination of Morphine and Its Principal Metabolites in Plasma Using High-Performance Liquid Chromatography and Fluorometric Detection

This article describes a high-performance liquid chromatography (HPLC) method for the simultaneous determination of morphine (M) and its principal metabolites morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), and normorphine (NM) in plasma. All four compounds are extracted from plasma using a C8 solid-phase extraction column, separated by reverse-phase HPLC on a C18 analytical column, and detected by spectrofluorometry at 210 nm excitation wavelength. The method takes advantage of the compounds' native fluorescence, so that derivitization is not required. Samples have been quantified over a concentration range of 25-100 ng/ml M and NM, 50-200 ng/ml M3G, and 100-300 ng/ml M6G, using nalorphine (500 ng/ml) as internal standard. Within-run and between-run errors were less than 10% for morphine and less than 13% for all the metabolites. The lower limit of quantitation for morphine is 10 ng/ml. The accuracy of the method was confirmed by including quality controls fitted to the standard curves of each compound. The assay described in this article represents a simplification of previous versions of the method, which included cumbersome extraction procedures and multiple detectors. For the first time, an internal standard has been employed. The assay is reliable and easy to use and can be performed in any therapeutic drug monitoring laboratory.

P-189 - Intracerebral drug concentration and monoamine metabolism: simultaneous determination of morphine and monoamine-related substances by HPLC-ECD

P-189 - Intracerebral drug concentration and monoamine metabolism: simultaneous determination of morphine and monoamine-related substances by HPLC-ECD

Simultaneous Determination of Morphine and Codeine in Blood by Use of Select Ion Monitoring and Deuterated Internal Standards

Simultaneous Determination of Morphine and Codeine in Blood by Use of Select Ion Monitoring and Deuterated Internal Standards

Simultaneous Determination of Morphine, Codeine, and Porphyroxine in Opium by Infrared and Visible Spectrometry.

Simultaneous Determination of Morphine, Codeine, and Porphyroxine in Opium by Infrared and Visible Spectrometry.