Quantitation of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in plasma and cerebrospinal fluid using solid-phase extraction and high-performance liquid chromatography with electrochemical detection.


:An original, sensitive, and specific high-performance liquid chromatographic (HPLC) assay was developed for the quantitation of morphine and its two major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), in human plasma and cerebrospinal fluid (CSF) and in rat plasma, using hydromorphone as the internal standard. Solid-phase extraction was used to separate morphine and its glucuronide metabolites from plasma constituents. Extraction efficiencies of morphine, M3G, and M6G from human plasma samples (0.5 ml) were 84, 87, and 88%, respectively. Extraction efficiencies of morphine, M3G, and M6G did not differ significantly (p > 0.05) between human plasma and CSF or rat plasma. Morphine, M3G, M6G, and hydromorphone were separated on a 10 mu C8 Resolve radially compressed cartridge using a mobile phase comprising methanol:acetonitrile:phosphate buffer, (0.0125M pH 7.5; 10:10:80), in which 11 mg/L of cetyltrimethylammonium bromide (cetrimide) was dissolved. Quantitation was achieved using a single electrochemical detector at ambient temperature (23 degrees C). Standard curves were linear over the ranges 0.020-2.190, 0.027-2.709, and 0.027-0.542 microM for morphine, M3G, and M6G, respectively. Lower limits of detection for morphine, M3G, and M6G in human plasma and CSF samples (0.5 ml) were 0.020, 0.027, and 0.027 microM, respectively. Corresponding lower limits of detection in rat plasma (0.1 ml) were 0.102, 0.135, and 0.135 microM, respectively. Intraassay precision for low and high concentrations of morphine, M3G, and M6G were < 23 and < 8% respectively. Similarly, interassay accuracy for low and medium concentrations of morphine, M3G, and M6G were < 17% and were < 9% for high concentrations.


Ther Drug Monit


Wright AW,Watt JA,Kennedy M,Cramond T,Smith MT




Has Abstract


1994-04-01 00:00:00












  • Effect of ofloxacin on the pharmacokinetics of a single intravenous theophylline dose.

    abstract::The effect of ofloxacin taken for 8 days (200 mg twice daily) on the pharmacokinetics of a single intravenous dose of theophylline (4.3 mg/kg over 15 min) was studied in a crossover procedure among seven healthy male volunteers. Theophylline concentrations were measured serially for 10 h by the immunofluorescence pola...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Al-Turk WA,Shaheen OM,Othman S,Khalaf RM,Awidi AS

    更新日期:1988-01-01 00:00:00

  • Measurement of lamotrigine under conditions measuring phenobarbitone, phenytoin, and carbamazepine using reversed-phase high-performance liquid chromatography at dual wavelengths.

    abstract::A reverse-phase high-performance liquid chromatographic (HPLC) method for the measurement of lamotrigine (LTG) simultaneously with phenobarbitone (PB), phenytoin (PHT), and carbamazepine (CBZ) is described using hexobarbital as the internal standard. The method uses the chromophore at 307 nm to detect LTG in the prese...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Ramachandran S,Underhill S,Jones SR

    更新日期:1994-02-01 00:00:00

  • Impact of Laboratory Practices on Interlaboratory Variability in Therapeutic Drug Monitoring of Immunosuppressive Drugs.

    abstract::The immunosuppressants cyclosporine, tacrolimus, sirolimus, everolimus, and probably also mycophenolic acid require therapeutic drug monitoring (TDM)-guided dosing to ensure that blood concentrations are kept within the target range in transplant patients. Reliable, accurate, and precise test methods are therefore ess...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Christians U,Vinks AA,Langman LJ,Clarke W,Wallemacq P,van Gelder T,Renjen V,Marquet P,Meyer EJ

    更新日期:2015-12-01 00:00:00

  • Plasma indomethacin assay using high-performance liquid chromatography-electrospray-tandem mass spectrometry: application to therapeutic drug monitoring and pharmacokinetic studies.

    abstract::The authors report the use of high-performance liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS) for the quantification of indomethacin (IND) in plasma with microscale sample preparation. Plasma samples (100 microL) and mefanamic acid (internal standard [IS]), buffered to pH 3.5, were prepar...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Taylor PJ,Jones CE,Dodds HM,Hogan NS,Johnson AG

    更新日期:1998-12-01 00:00:00

  • Therapeutic drug monitoring of voriconazole in a child with invasive aspergillosis requiring extracorporeal membrane oxygenation.

    abstract::We describe a patient with invasive pulmonary aspergillosis on extracorporeal membrane oxygenation therapy in which therapeutic drug monitoring and individualization of therapy by measuring voriconazole plasma concentrations were performed. ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Brüggemann RJ,Antonius T,Heijst Av,Hoogerbrugge PM,Burger DM,Warris A

    更新日期:2008-12-01 00:00:00

  • Mycophenolic acid plasma concentrations: influence of comedication.

    abstract::Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred f...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章


    authors: Pou L,Brunet M,Cantarell C,Vidal E,Oppenheimer F,Monforte V,Vilardell J,Roman A,Martorell J,Capdevila L

    更新日期:2001-02-01 00:00:00

  • Quantification of immunosuppression by flow cytometry in stable renal transplant recipients.

    abstract::The current standard of monitoring transplant patients by drug levels is not optimal because it does not take into account the different and individual effects of immunosuppressive drugs on each patient. In this study, the authors tested immune function assays for monitoring transplant patients. Blood was collected fr...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Stalder M,Bîrsan T,Holm B,Haririfar M,Scandling J,Morris RE

    更新日期:2003-02-01 00:00:00

  • Roxithromycin-induced toxic epidermal necrolysis.

    abstract::This case report highlights a very rare adverse drug reaction of oral roxithromycin causing toxic epidermal necrolysis (TEN). A 54-year-old male patient diagnosed with upper respiratory tract infection was prescribed oral roxithromycin 150 mg twice daily for 7 days. On the 10th day, the patient was admitted to the eme...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Das S,Mondal S,Dey JK

    更新日期:2012-08-01 00:00:00

  • Subtherapeutic Linezolid Concentration in a Patient With Bullous Pemphigoid Complicated by Methicillin-Resistant Staphylococcus aureus Infection: A Case Study.

    abstract::We presented a case of subtherapeutic linezolid concentration in a patient with bullous pemphigoid characterized by large area skin anabrosis complicated by methicillin-resistant Staphylococcus aureus infections. ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Chen C,Zhang M,Chen H,Fang J

    更新日期:2020-08-01 00:00:00

  • Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral fluid, and sweat during treatment of opioid-dependent pregnant women.

    abstract:BACKGROUND:Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high-dose (14-20 mg...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,随机对照试验


    authors: Concheiro M,Jones HE,Johnson RE,Choo R,Huestis MA

    更新日期:2011-10-01 00:00:00

  • Valproate monotherapy in juvenile myoclonic epilepsy: dose-related effects on electroencephalographic and other neurophysiologic tests.

    abstract::A neurophysiologic test battery (consisting of a 24-hour, seven-channel electroencephalogram [EEG], EEG spectral analysis, multiple sleep latency test, visual evoked potentials, critical flicker fusion, and visual contrast sensitivity) was administered twice to 16 patients with juvenile myoclonic epilepsy (JME) in a d...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Sundqvist A,Nilsson BY,Tomson T

    更新日期:1999-02-01 00:00:00

  • Individualized dosing of enoxaparin for subjects with renal impairment is superior to conventional dosing at achieving therapeutic concentrations.

    abstract:INTRODUCTION:Enoxaparin is an anticoagulant used in the treatment of thromboembolic diseases. It is a hydrophilic molecule that is, predominantly, eliminated renally with few data to support dosing for subjects with renal impairment and/or obesity. A recently conducted randomized controlled clinical trial compared indi...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,随机对照试验


    authors: Barras MA,Duffull SB,Atherton JJ,Green B

    更新日期:2010-08-01 00:00:00

  • Light-induced racemization: artifacts in the analysis of the diastereoisomeric pairs of thioridazine 5-sulfoxide in the plasma and urine of patients treated with thioridazine.

    abstract::The ring sulfoxidation of thioridazine (THD), a widely used neuroleptic agent, yields two diastereoisomeric pairs, fast- and slow-eluting (FE and SE) thioridazine 5-sulfoxide (THD 5-SO). Until now, studies in which concentrations of these metabolites were measured in THD-treated patients have revealed no significant d...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Eap CB,Souche A,Koeb L,Baumann P

    更新日期:1991-07-01 00:00:00

  • Serum Concentrations of Paliperidone After Administration of the Long-Acting Injectable Formulation.

    abstract:BACKGROUND:The pharmacokinetics of long-acting intramuscular paliperidone in a naturalistic setting is not well documented. The objective of this study was to investigate the relationship between dose and serum concentrations of paliperidone using data from a routine therapeutic drug monitoring service. METHODS:Serum ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Helland A,Spigset O

    更新日期:2017-12-01 00:00:00

  • Potential of Oral Fluid as a Clinical Specimen for Compliance Monitoring of Psychopharmacotherapy.

    abstract:BACKGROUND:Oral fluid (OF) is being developed as a specimen for the determination of drug intake as an alternative to serum and plasma. It is generally considered as an attractive specimen due to the noninvasive nature of the sampling procedure and the relation to the free fraction of drug in the blood. These features ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Neumann J,Beck O,Dahmen N,Böttcher M

    更新日期:2018-04-01 00:00:00

  • Excretion of the principal urinary metabolites of phenytoin and absolute oral bioavailability determined by use of a stable isotope in patients with epilepsy.

    abstract:BACKGROUND:The anticonvulsant properties of phenytoin (PHT) were discovered in 1938. Since then, it has been one of the most widely used antiepileptic drugs. It is slowly absorbed, extensively plasma protein-bound, exhibits a nonlinear, concentration-dependent pharmacokinetic profile, and has a narrow therapeutic range...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Aliwarga T,Cloyd JC,Goel V,Brundage RC,Marino SE,Leppik IE,Remmel RP

    更新日期:2011-02-01 00:00:00

  • Dosage adjustment of high-dose methotrexate using Bayesian estimation: a comparative study of two different concentrations at the end of 8-h infusions.

    abstract::Bayesian estimation (BE) of pharmacokinetic parameters enables the clinician to adjust the dosage of high-dose methotrexate (HDMTX) to correct the inter- and intraindividual variation of concentrations that are responsible for severe toxicity. In this study of 672 HDMTX infusions, we validated an approach that consist...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Pignon T,Lacarelle B,Duffaud F,Guillet P,Catalin J,Durand A,Favre R

    更新日期:1995-10-01 00:00:00

  • Effects of hepatic function on vancomycin pharmacokinetics in patients with cancer.

    abstract::Vancomycin is widely used in the prophylaxis and treatment of infections in neutropenic patients with cancer. The objective of this study was to analyze liver damage effects on vancomycin pharmacokinetics and determine the necessity for liver function evaluation when selecting vancomycin dosing schedules in these pati...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Aldaz A,Ortega A,Idoate A,Giráldez J,Brugarolas A

    更新日期:2000-06-01 00:00:00

  • No pharmacokinetic but pharmacodynamic interactions between cisapride and bromperidol or haloperidol.

    abstract::Pharmacokinetic and pharmacodynamic interactions between the gastrokinetic drug cisapride and the antipsychotic drugs bromperidol and haloperidol were studied in 29 schizophrenic inpatients. Fourteen patients were taking bromperidol (12-24 mg/d), and 15 were taking haloperidol (12-36 mg/d). Cisapride 10 mg/d was coadm...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章


    authors: Mihara K,Otani K,Yasui N,Ishida M,Kondo T,Suzuki A,Furukori H,Nagashima U,Kaneko S,Inoue Y

    更新日期:1999-06-01 00:00:00

  • Cyclosporine monitoring in renal transplantation: area under the curve monitoring is superior to trough-level monitoring.

    abstract::Trough levels (TL) of cyclosporine (CS) measured in serum by the polyclonal radioimmunoassay (SR) are useful for dissecting the etiology of clinical events, but they are a poor guide to dosage adjustments. In renal transplant patients immunosuppressed by low doses of prednisone and CS given orally, once-a-day TL (24-h...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Grevel J,Welsh MS,Kahan BD

    更新日期:1989-01-01 00:00:00

  • Sensitive determination of itraconazole and its active metabolite in human plasma by column-switching high-performance liquid chromatography with ultraviolet detection.

    abstract::A simple and sensitive column-switching high-performance liquid chromatographic method for the simultaneous determination of itraconazole (ITZ) and its active metabolite, hydroxyitraconazole (HIT) in human plasma is described. ITZ, HIT, and an internal standard, R051012, were extracted from 1 mL of alkalinized plasma ...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章


    authors: Uno T,Shimizu M,Sugawara K,Tateishi T

    更新日期:2006-08-01 00:00:00

  • Population Pharmacokinetic Analysis of Meropenem in Critically Ill Patients With Acute Kidney Injury Treated With Continuous Hemodiafiltration.

    abstract:BACKGROUND:The aim of this study was to conduct a population pharmacokinetic (PK) analysis of meropenem and to explore the optimal dosing strategy for meropenem in critically ill patients with acute kidney injury receiving treatment with continuous hemodiafiltration (CHDF). METHODS:Blood samples were obtained on days ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Niibe Y,Suzuki T,Yamazaki S,Suzuki T,Takahashi N,Hattori N,Nakada TA,Oda S,Ishii I

    更新日期:2020-08-01 00:00:00

  • Liquid chromatographic determination of piroxicam in serum.

    abstract::A sensitive method for monitoring serum piroxicam (Feldene) is described. The assay requires 1.0 ml of specimen and involves chloroform extraction from an acidified mixture followed by concentration and injection into a liquid chromatograph. Column effluent is monitored at 330 nm. Retention times of piroxicam and the ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Fraser AD,Woodbury JF

    更新日期:1983-06-01 00:00:00

  • Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia.

    abstract::This study explored the association of 14 single nucleotide polymorphisms in three genes coding for influx transporters (SLC22A1, SLCO1B1, and SLCO1B3), two genes coding for efflux transporters (ABCB1 and ABCG2), and four genes coding for enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A5) with the pharmacokinetics of imati...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Yamakawa Y,Hamada A,Nakashima R,Yuki M,Hirayama C,Kawaguchi T,Saito H

    更新日期:2011-04-01 00:00:00

  • Therapeutic Drug Monitoring Can Improve Linezolid Dosing Regimens in Current Clinical Practice: A Review of Linezolid Pharmacokinetics and Pharmacodynamics.

    abstract::Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and ne...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Rao GG,Konicki R,Cattaneo D,Alffenaar JW,Marriott DJE,Neely M,IATDMCT Antimicrobial Scientific Committee.

    更新日期:2020-02-01 00:00:00

  • Vancomycin Area Under the Curve Simplified.

    abstract:BACKGROUND:Serum trough concentrations as the sole means of monitoring safety and efficacy of vancomycin are insufficient. The daily area under the curve (AUC24) of serum concentration versus time to minimum inhibitory concentration (MIC) ratio of greater than 400 mg × h/L has emerged as a more robust dosing target. A ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Lewis P

    更新日期:2018-06-01 00:00:00

  • A clinically useful capillary blood-sampling technique for rapid determination of therapeutic levels of theophylline.

    abstract::Two blood-sampling techniques, capillary and venous, were compared using the EMIT method. No difference was found in reproducibility. However, persistent positive bias of 0.628 micrograms/ml (p less than 0.01) was noted with the capillary sampling method. Any hemolysis that occurred in the capillary sampling technique...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Frazer JF 3rd,Stasiowski P,Boyd GK

    更新日期:1983-01-01 00:00:00

  • No influence of body weight on serum levels of antidepressants.

    abstract:BACKGROUND:Body weight may affect pharmacokinetic parameters in various ways and may therefore have a significant impact on the serum concentration of a drug at a given dose. Although patients with major depressive disorder frequently show an elevated body mass index, studies investigating the relation between body wei...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Unterecker S,Deckert J,Pfuhlmann B

    更新日期:2011-12-01 00:00:00

  • Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

    abstract:BACKGROUND:Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Noll BD,Coller JK,Somogyi AA,Morris RG,Russ GR,Hesselink DA,Van Gelder T,Sallustio BC

    更新日期:2013-10-01 00:00:00

  • No increase in carbamazepine-10,11-epoxide during addition of lamotrigine treatment in children.

    abstract::It has been suggested that lamotrigine (LTG) may enhance the toxicity of carbamazepine (CBZ) by increasing the concentration of the active metabolite carbamazepine-10,11-epoxide (CBZ-E) in adult patients. The authors investigated this hypothesis in an add-on study in 11 children and 3 adolescents, aged 6-22 years, who...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Eriksson AS,Boreus LO

    更新日期:1997-10-01 00:00:00