Quantitative determination of total methamphetamine and active metabolites in rat tissue by liquid chromatography with tandem mass spectrometric detection

Hendrickson, Howard P.; Laurenzana, Elizabeth M.; Owens, S. Michael

doi:10.1208/aapsj080480

Cited by 30 publications

(30 citation statements)

References 49 publications

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“…Determination of METH and AMP concentration in rat serum was based on the liquid-liquid phase extraction (LLE) method developed by Hendrickson et al (2006). In brief, 25 or 50 l of each serum sample was diluted to 100 l using drug-free normal rat serum (Pel-Freez Biologicals, Rogers, AR).…”

Section: Methodsmentioning

confidence: 99%

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Gestation Time-Dependent Pharmacokinetics of Intravenous (+)-Methamphetamine in Rats

White

Laurenzana²,

Hendrickson³

et al. 2011

Drug Metab Dispos

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ABSTRACT:We tested the hypothesis that differences in (؉)-methamphetamine (METH) disposition during late rat pregnancy could lead to increased vulnerability to acute METH effects. The disposition of a single 1 mg/kg i.v. METH dose was studied during early (gestation day 7, GD7) and late (GD21) gestation. Results showed gestation time-dependent pharmacokinetics, characterized by a significantly higher area under the METH serum concentration versus time curve and a lower clearance on GD21 (p < 0.05; total, renal, and nonrenal clearance). The terminal elimination half-life (t 1/2z ) of METH and (؉)-amphetamine (AMP; a pharmacologically active metabolite of METH) were not different on GD7, but by GD21, AMP t 1/2z was 37% longer than METH t 1/2z (p < 0.05). To identify the mechanism for AMP metabolite changes, intravenous AMP pharmacokinetics on GD21 were compared with AMP metabolite pharmacokinetics after intravenous METH. The intravenous AMP t 1/2z was significantly shorter than metabolite AMP t 1/2z (p < 0.05), which suggested AMP metabolite formation (not elimination) was the rate-limiting process. To understand the medical consequence of METH use during late-stage pregnancy, timed-pregnant rats received an intravenous dose of saline or METH (1, 3, or 5.6 mg/kg) on GD21, 0 to 2 days antepartum. Although one rat died and another had stillbirths at term after the 5.6-mg/kg dose, the pharmacokinetic values for all of the other animals were not significantly different. In conclusion, late-gestational clearance reductions lengthen METH exposure time, possibly increasing susceptibility to adverse effects, including death.

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Section: Methodsmentioning

confidence: 99%

“…The drug-containing solutions from LLE were injected (20 l) onto a 3-m BDS Hypersil C8 column (Thermo Fisher Scientific) and analytically separated using a binary linear gradient (Hendrickson et al, 2006). The flow rate was 0.3 ml/min.…”

Section: Methodsmentioning

confidence: 99%

Gestation Time-Dependent Pharmacokinetics of Intravenous (+)-Methamphetamine in Rats

White

Laurenzana²,

Hendrickson³

et al. 2011

Drug Metab Dispos

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“…Serum samples were prepared as described above and stored at Ϫ20°C until analyzed. PCP was extracted from serum by liquidphase extraction, using a simple trichloroacetic acid treatment as described previously for METH (Hendrickson et al, 2006). PCP concentrations (ng/ml) in serum samples were determined by liquid chromatography with tandem mass spectrometry detection (LC-MS/ MS), as described previously (Hendrickson et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

The Fate and Function of Therapeutic Antiaddiction Monoclonal Antibodies across the Reproductive Cycle of Rats

Hubbard¹,

Laurenzana²,

Williams³

et al. 2010

J Pharmacol Exp Ther

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During preclinical development of neuroprotective antiaddiction therapeutic monoclonal antibodies (mAbs) against phencyclidine (PCP) and (ϩ)-methamphetamine, we discovered novel, gestation stage-specific changes in mAb disposition spanning the entire reproductive cycle of female rats. Each pharmacological change was independent of mAb dose and antigen target but was precisely coincident with transitions between the gestational trimesters, parturition, and lactation periods of the female reproductive cycle. Whereas anti-PCP mAb6B5 terminal elimination half-life (t 1/2z ) in nonpregnant females was 6.6 Ϯ 1.6 days, the mAb6B5 t 1/2z significantly changed to 3.7 Ϯ 0.4 days, then 1.4 Ϯ 0.1 days, then 3.0 Ϯ 0.4 days in the second trimester, third trimester, and postpartum periods, respectively (p Ͻ 0.05 for each change). Initially, these evolving changes in mAb6B5 clearance (3.3-fold), distribution volume (1.8-fold), and elimination half-life (4.7-fold) affected our ability to sustain sufficient mAb6B5 levels to sequester PCP in the bloodstream. However, understanding the mechanisms underlying each transition allowed development of an adaptive mAb-dosing paradigm, which substantially reduced PCP levels in dam brains and fetuses throughout pregnancy. These mAb functional studies also revealed that antidrug mAbs readily cross the placenta before syncytiotrophoblast barrier maturation, demonstrating the dynamic nature of mAb pharmacokinetics in pregnancy and the importance of maintaining maternal mAb levels. These studies provide the first preclinical pregnancy model in any species for chronic mAb dosing and could have important implications for the use of antibody therapies involving blood organ barriers (such as addiction) or other chronic diseases in women of childbearing age (e.g., irritable bowel diseases, multiple sclerosis, breast cancer, rheumatoid arthritis).

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“…METH and AMP serum concentrations were determined using LC-MS/MS methodology published previously (Hendrickson et al 2006). A Waters Alliance 2690 HPLC system coupled to a Micromass Quattro LC triple quadrupole mass spectrometer (Waters Corp, Beverly MA) was used for LC-MS/MS analysis.…”

Section: Lc-ms/ms Of Meth Amp and 4-hydroxylated Metabolites In Serummentioning

confidence: 99%

Bioavailability of (+)-methamphetamine in the pigeon following an intramuscular dose

Hendrickson

Hardwick

McMillan

et al. 2008

Pharmacology Biochemistry and Behavior

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Pigeons are used frequently as subjects in behavioral pharmacology research. An advantage of the pigeon is an exceedingly vascular breast muscle, which is easily accessible for injections. The purpose of these studies was to provide a profile of the pharmacokinetics of (+)-methamphetamine (METH) and (+)-amphetamine (AMP), a pharmacologically active metabolite, in pigeons (n = 6) after intramuscular (IM) and intravenous (IV) dosing (0.8 mg/kg). LC-MS/MS analysis was used to determine serum concentrations of METH and AMP. A modified crossover design was used to determine the bioavailability, time to maximum concentration, total clearance, the volume of distribution, the maximal concentration, the area under the concentration-time curve (AUC), and terminal elimination half-life for METH. The route of administration did not significantly affect these pharmacokinetic parameters. The time to maximum concentration for METH and AMP following IM administration was 0.3 h. Maximum AMP serum concentrations were achieved in 2 h, irrespective of the route of administration, and these concentrations remained essentially constant for an additional 6 h. The metabolism of METH to AMP was not affected by the route of administration, and the molar ratio AMP to METH AUC values were the same (IV=0.57; IM=0.41). These results show that METH pharmacokinetics after IM administration in the pigeon are similar to IV administration. Thus IM is a reasonable route of administration for METH behavioral assays in the pigeon if sufficient time for absorption is given following the dose, and the behavioral endpoint is not dependent on the rapid input of METH following an IV dose.

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Quantitative determination of total methamphetamine and active metabolites in rat tissue by liquid chromatography with tandem mass spectrometric detection

Cited by 30 publications

References 49 publications

Gestation Time-Dependent Pharmacokinetics of Intravenous (+)-Methamphetamine in Rats

Gestation Time-Dependent Pharmacokinetics of Intravenous (+)-Methamphetamine in Rats

The Fate and Function of Therapeutic Antiaddiction Monoclonal Antibodies across the Reproductive Cycle of Rats

Bioavailability of (+)-methamphetamine in the pigeon following an intramuscular dose

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