The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Gwendolyn A Mcmillin - One of the best experts on this subject based on the ideXlab platform.
-
simultaneous uplc ms ms assay for the detection of the traditional antipsychotics haloperidol fluphenazine perphenazine and Thiothixene in serum and plasma
Clinica Chimica Acta, 2013Co-Authors: Joetta M Juenke, Paul I Brown, Francis M Urry, Kamisha L Johnsondavis, Gwendolyn A McmillinAbstract:Abstract Background Most antipsychotic drugs that are commonly prescribed in the USA are monitored by liquid and gas chromatographic methods. Method performance has been improved using ultra high pressure liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). A rapid and simple procedure for monitoring haloperidol, Thiothixene, fluphenazine, and perphenazine is described here. Method Antipsychotic drug concentrations in serum and plasma were determined by LCMS/MS (Waters Acquity UPLC TQD). The instrument is operated with an ESI interface, in multiple reaction monitoring (MRM), and positive ion mode. The resolution of both quadrupoles was maintained at unit mass with a peak width at half height of 0.7 amu. Data analysis was performed using the Waters Quanlynx software. Serum or plasma samples were thawed at room temperature and a 100 μL aliquot was placed in a tube. Then 300 μL of precipitating reagent (acetonitrile-methanol [50:50, volume: volume]) containing the internal standard (0.12 ng/μL Imipramine-D3) was added to each tube. The samples were vortexed and centrifuged. The supernatant was transferred to an autosampler vial and 8 μL was injected into the UPLC–MS/MS. Utilizing a Waters Acquity UPLC HSS T3 1.8 μm, 2.1 × 50 mm column at 25 oC, the analytes were separated using a timed, linear gradient of acetonitrile and water, each having 0.1% formic acid added. The column is eluted into the LC–MS/MS to detect imipramine D3 at transition 284.25 > 89.10, haloperidol at 376.18 > 165.06, Thiothixene at 444.27 > 139.24, fluphenazine at 438.27 > 171.11, and perphenazine at 404.19 > 143.07. Secondary transitions for each analyte are also monitored for imipramine D3 at 284.25 > 193.10, haloperidol at 376.18 > 122.97, Thiothixene at 444.27 > 97.93, fluphenazine at 438.27 > 143.08, and perphenazine at 404.19 > 171.11. The run-time is 1.8 min per injection with baseline resolved chromatographic separation. Results: The analytical measurement range was 0.2 to 12.0 ng/mL for fluphenazine and perphenazine, and was 1 to 60.0 ng/mL for haloperidol and Thiothixene. Intra-assay and inter-assay imprecisions (CV) were less than 15% at two concentrations for each analyte. Conclusions By utilizing a LC–MS/MS method we combined two previously established analytical assays into one, yielding a 75% time-savings on set-up, and a significantly shortened analytical run-time. These changes reduced the turn-around time for analysis and eliminated interference issues resulting in fewer injections and increased column lifetime.
Kamisha L Johnsondavis - One of the best experts on this subject based on the ideXlab platform.
-
quantitation of haloperidol fluphenazine perphenazine and Thiothixene in serum or plasma using liquid chromatography tandem mass spectrometry lc ms ms
Methods of Molecular Biology, 2016Co-Authors: Matthew H Slawson, Kamisha L JohnsondavisAbstract:Haloperidol, fluphenazine, perphenazine, and Thiothixene are "typical" antipsychotic drugs that are used in the treatment of schizophrenia and other psychiatric disorders. The monitoring of the use of these drugs has applications in therapeutic drug monitoring and overdose situations. LC-MS/MS is used to analyze plasma/serum extracts with deuterated analog of imipramine as the internal standard to ensure accurate quantitation and control for any potential matrix effects. Positive ion electrospray is used to introduce the analytes into the mass spectrometer. Selected reaction monitoring of two product ions for each analyte allows for the calculation of ion ratios which ensures correct identification of each analyte, while a matrix-matched calibration curve is used for quantitation.
-
simultaneous uplc ms ms assay for the detection of the traditional antipsychotics haloperidol fluphenazine perphenazine and Thiothixene in serum and plasma
Clinica Chimica Acta, 2013Co-Authors: Joetta M Juenke, Paul I Brown, Francis M Urry, Kamisha L Johnsondavis, Gwendolyn A McmillinAbstract:Abstract Background Most antipsychotic drugs that are commonly prescribed in the USA are monitored by liquid and gas chromatographic methods. Method performance has been improved using ultra high pressure liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). A rapid and simple procedure for monitoring haloperidol, Thiothixene, fluphenazine, and perphenazine is described here. Method Antipsychotic drug concentrations in serum and plasma were determined by LCMS/MS (Waters Acquity UPLC TQD). The instrument is operated with an ESI interface, in multiple reaction monitoring (MRM), and positive ion mode. The resolution of both quadrupoles was maintained at unit mass with a peak width at half height of 0.7 amu. Data analysis was performed using the Waters Quanlynx software. Serum or plasma samples were thawed at room temperature and a 100 μL aliquot was placed in a tube. Then 300 μL of precipitating reagent (acetonitrile-methanol [50:50, volume: volume]) containing the internal standard (0.12 ng/μL Imipramine-D3) was added to each tube. The samples were vortexed and centrifuged. The supernatant was transferred to an autosampler vial and 8 μL was injected into the UPLC–MS/MS. Utilizing a Waters Acquity UPLC HSS T3 1.8 μm, 2.1 × 50 mm column at 25 oC, the analytes were separated using a timed, linear gradient of acetonitrile and water, each having 0.1% formic acid added. The column is eluted into the LC–MS/MS to detect imipramine D3 at transition 284.25 > 89.10, haloperidol at 376.18 > 165.06, Thiothixene at 444.27 > 139.24, fluphenazine at 438.27 > 171.11, and perphenazine at 404.19 > 143.07. Secondary transitions for each analyte are also monitored for imipramine D3 at 284.25 > 193.10, haloperidol at 376.18 > 122.97, Thiothixene at 444.27 > 97.93, fluphenazine at 438.27 > 143.08, and perphenazine at 404.19 > 171.11. The run-time is 1.8 min per injection with baseline resolved chromatographic separation. Results: The analytical measurement range was 0.2 to 12.0 ng/mL for fluphenazine and perphenazine, and was 1 to 60.0 ng/mL for haloperidol and Thiothixene. Intra-assay and inter-assay imprecisions (CV) were less than 15% at two concentrations for each analyte. Conclusions By utilizing a LC–MS/MS method we combined two previously established analytical assays into one, yielding a 75% time-savings on set-up, and a significantly shortened analytical run-time. These changes reduced the turn-around time for analysis and eliminated interference issues resulting in fewer injections and increased column lifetime.
Rajiv Tandon - One of the best experts on this subject based on the ideXlab platform.
-
the effect of paroxetine on Thiothixene pharmacokinetics
Journal of Clinical Pharmacy and Therapeutics, 1997Co-Authors: Sally K Guthrie, M Hariharan, A A Kumar, G Bader, Rajiv TandonAbstract:SUMMARY Objective: In this study healthy volunteers received Thiothixene with and without a 3-day pretreatment with paroxetine to determine if paroxetine decreased the clearance of Thiothixene. Method: Ten healthy medication-free volunteers (4 women and 6 men, mean age 38&12 years) were randomized to receive a single 20 mg oral dose of Thiothixene on two separate occasions. On one occasion Thiothixene was given concurrently, and following 3 days of pre-treatment with oral paroxetine (20 mg/day). On the other occasion Thiothixene was given without paroxetine pretreatment. The two study days were separated by a minimum period of 2 weeks. On both study days, after the administration of Thiothixene, 10 ml blood samples were collected over the next 72 h. Results: None of the pharmacokinetic parameters of Thiothixene were significantly altered by a 3-day treatment with paroxetine. Discussion: It is likely that the CYP2D6 isoenzyme is not responsible for a high proportion of Thiothixene clearance, but one cannot exclude the possibility that a longer paroxetine pretreatment might have caused some inhibition of Thiothixene clearance.
-
a simple sensitive liquid chromatographic assay of cis Thiothixene in plasma with coulometric detection
Therapeutic Drug Monitoring, 1991Co-Authors: M Hariharan, Ted Vannoord, Erick K Kindt, Rajiv TandonAbstract:A novel, simple, and very sensitive liquid-chromatographic assay with a coulometric detector has been developed for quantitating cis-Thiothixene (CTX) in human plasma. A reverse phase, 5-microns cyano column (25 x 0.46 cm), a mobile phase of phosphate buffer (pH 2.5) and acetonitrile (40/60 by vol), and a coulometric detector are used for the separation of CTX, and the internal standard, trifluoperazine. CTX and trifluoperazine are extracted from alkalinized plasma into n-pentane-isopropanol (95/5 by vol) and purified by back extraction into perchloric acid. The optimum oxidation potential for the analytes is +0.8 V versus an Ag/AgCl electrode. The detection limit for CTX is 200 pg using 1 mL of plasma and CTX concentrations are linear from 0 to 40 micrograms/L. The average interassay CV is 9%, and the mean recovery is 99% relative to the internal standard. Possible interferences from various psychiatric and common drugs in the assay have been studied. The assay method was validated by determining the concentration of CTX in the plasma of 100 schizophrenic patients.
Kamal K. Midha - One of the best experts on this subject based on the ideXlab platform.
-
cis flupentixol metabolites in rat plasma and bile the first proof of glutathione conjugation at the exocyclic double bond
Drug Metabolism and Disposition, 1991Co-Authors: J W Hubbard, Emily M. Hawes, Gordon Mckay, Kamal K. MidhaAbstract:The plasma and biliary metabolites of cis-flupentixol (cis-FPT) were studied after ip administration to rats. Cis-FPT sulfoxide was found to be the major phase-I metabolite in plasma and bile. Five biliary metabolites were isolated by gradient elution HPLC and characterized by various spectroscopic methods: F1, 19-S-glutathionyl-10,19-dihydroFPT sulfoxide; F2, cis-FPT sulfoxide sulfate; F3, 8-O-(or 7-O) glucuronyl-cis-FPT; F4, cis-FPT sulfoxide; and F5, cis-FPT glucuronide. A novel non-enzymatic addition of glutathione (GSH) onto the exocyclic double bond was demonstrated to occur for the first time with not only flupentixol and certain of its metabolites, but also with other psychotropic drugs with a tricyclic nucleus and an exocyclic double bond. Specifically, these nonenzymatic additions of GSH were observed with cis-FPT, trans-FPT, cis-FPT sulfoxide, cis-, trans-dealkylFPT, cis-FPT N-oxide, cis-chlorprothixene, cis-Thiothixene, and cyclobenzaprine. Among them, cis-FPT sulfoxide showed the most potent adduct formation activity, and the product was characterized to be identical with the in vivo metabolite F1 of cis-FPT.
Joetta M Juenke - One of the best experts on this subject based on the ideXlab platform.
-
simultaneous uplc ms ms assay for the detection of the traditional antipsychotics haloperidol fluphenazine perphenazine and Thiothixene in serum and plasma
Clinica Chimica Acta, 2013Co-Authors: Joetta M Juenke, Paul I Brown, Francis M Urry, Kamisha L Johnsondavis, Gwendolyn A McmillinAbstract:Abstract Background Most antipsychotic drugs that are commonly prescribed in the USA are monitored by liquid and gas chromatographic methods. Method performance has been improved using ultra high pressure liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). A rapid and simple procedure for monitoring haloperidol, Thiothixene, fluphenazine, and perphenazine is described here. Method Antipsychotic drug concentrations in serum and plasma were determined by LCMS/MS (Waters Acquity UPLC TQD). The instrument is operated with an ESI interface, in multiple reaction monitoring (MRM), and positive ion mode. The resolution of both quadrupoles was maintained at unit mass with a peak width at half height of 0.7 amu. Data analysis was performed using the Waters Quanlynx software. Serum or plasma samples were thawed at room temperature and a 100 μL aliquot was placed in a tube. Then 300 μL of precipitating reagent (acetonitrile-methanol [50:50, volume: volume]) containing the internal standard (0.12 ng/μL Imipramine-D3) was added to each tube. The samples were vortexed and centrifuged. The supernatant was transferred to an autosampler vial and 8 μL was injected into the UPLC–MS/MS. Utilizing a Waters Acquity UPLC HSS T3 1.8 μm, 2.1 × 50 mm column at 25 oC, the analytes were separated using a timed, linear gradient of acetonitrile and water, each having 0.1% formic acid added. The column is eluted into the LC–MS/MS to detect imipramine D3 at transition 284.25 > 89.10, haloperidol at 376.18 > 165.06, Thiothixene at 444.27 > 139.24, fluphenazine at 438.27 > 171.11, and perphenazine at 404.19 > 143.07. Secondary transitions for each analyte are also monitored for imipramine D3 at 284.25 > 193.10, haloperidol at 376.18 > 122.97, Thiothixene at 444.27 > 97.93, fluphenazine at 438.27 > 143.08, and perphenazine at 404.19 > 171.11. The run-time is 1.8 min per injection with baseline resolved chromatographic separation. Results: The analytical measurement range was 0.2 to 12.0 ng/mL for fluphenazine and perphenazine, and was 1 to 60.0 ng/mL for haloperidol and Thiothixene. Intra-assay and inter-assay imprecisions (CV) were less than 15% at two concentrations for each analyte. Conclusions By utilizing a LC–MS/MS method we combined two previously established analytical assays into one, yielding a 75% time-savings on set-up, and a significantly shortened analytical run-time. These changes reduced the turn-around time for analysis and eliminated interference issues resulting in fewer injections and increased column lifetime.