Alteration in cytochrome P450 3A4 activity as measured by a urine cortisol assay in HIV-1-infected pregnant women and relationship to antiretroviral pharmacokinetics.

Objectives: Pregnancy results in physiological changes altering the pharmacokinetics of drugs metabolized by cytochrome P450 3A4 (CYP3A4). The urinary ratio of 6-β hydroxycortisol to cortisol (6βHF : F) is a marker of CYP3A4 induction. We sought to evaluate its change in antiretroviral (ARV)-treated HIV-1-infected women and to relate this change to ARV pharmacokinetics.

Raltegravir pharmacokinetics during pregnancy.

Objective: We evaluated the pharmacokinetics (PK) of raltegravir in HIV-infected women during pregnancy and postpartum.

Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is an ongoing prospective study of antiretroviral PK during pregnancy (NCT00042289). Women receiving 400 mg raltegravir twice daily in combination antiretroviral therapy had intensive steady-state 12-hour PK profiles performed during pregnancy and at 6- to 12-week postpartum.

Determination of meropenem in bacterial media by LC-MS/MS.

To support the development of a dynamic in vitro human pharmacokinetic/pharmacodynamic simulation model for biofilm-mediated infections and study stability of meropenem, an LC-MS/MS method for the determination of meropenem in Luria Bertani (LB) media was developed and validated in an API2000 LC-MS/MS system. A partial validation was also performed in M9 media. Sample aliquots of 100μL (or 25μL for M9 media) were mixed with the internal standard (IS) ceftazidime and filtered.

Simultaneous determination of fludarabine and clofarabine in human plasma by LC-MS/MS.

A method for quantification of fludarabine (FDB) and clofarabine (CFB) in human plasma was developed with an API5000 LC-MS/MS system. FDB and CFB were extracted from EDTA plasma samples by protein precipitation with trichloroacetic acid. Briefly, 50 μL plasma sample was mixed with 25 μL internal standard (50 ng/mL aqueous 2-Cl-adensosine) and 25 μL 20% trichloroacetic acid, centrifuged at 25,000 × g (20,000 rpm) for 3 min, and then transfered to an autosampler vial.

Determination of intracellular fludarabine triphosphate in human peripheral blood mononuclear cells by LC-MS/MS.

Fludarabine is a nucleoside analog routinely used in conditioning regimens of pediatric allogeneic stem cell transplantation to promote stem cell engraftment. In children, it remains a challenge to accurately and precisely quantify the active intracellular triphosphate species of fludarabine in vivo, primarily due to limitations on blood volume and inadequate assay sensitivity. Here we report a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determination of fludarabine triphosphate in human peripheral blood mononuclear cells (PBMC).