Background and objectives Although indomethacin has been widely used for the treatment of preterm labor over the past 40 years, there are few reports regarding its pharmacokinetics in pregnant women. Methods This opportunistic study assessed the steady-state pharmacokinetics of indomethacin in pregnant subjects to whom an oral dose of 25 mg every 6 h was prescribed. Indomethacin concentrations in plasma and urine were analyzed by a validated high-performance liquid chromatography method with mass spectrometric detection. Results The mean area under the plasma concentration versus time curve at steady state (AUCss) was 1.91 ± 0.53 lg h/mL, mean peak plasma concentration (Cmax) was 1.02 ± 0.49 lg/mL, and mean time to reach Cmax (tmax) was 1.3 ± 0.7 h. The mean apparent clearance at steady state was 14.5 ± 5.5 L/h, which is higher than the apparent clearance reported in the literature for non-pregnant subjects. Indomethacin crosses the placenta; the mean fetal/maternal ratio from five sets of cord blood samples collected at delivery was 4.0 ± 1.1. Conclusions Further studies are needed to determine whether any dose adjustments are necessary as a result of the increased clearance of indomethacin during pregnancy.

A liquid chromatography in tandem with electro-spray ionization mass spectrometry method has been developed and validated for the quantitative determination of BUP and its major metabolites (hydroxybupropion, threo- and erythrohydrobupropion) in human umbilical cord plasma and placental tissue. The samples were acidified with trichloroacetic acid, and protein precipitated by adding acetonitrile. Chromatographic separation of drug and metabolites was achieved by using a Waters Symmetry C18 column, with an isocratic elution of 31% methanol and 69% formic acid (0.04%, v/v) aqueous solution at a flow rate of 1.0 mL/min. Detection was carried out by mass spectrometry using positive electro-spray ionization mode, and the compounds were monitored using multiple reactions monitoring method. Deuterium-labeled isotopes of the compounds were used as internal standards. Calibration curves were linear (r2 >0.99) in the tested ranges. The lower limit of quantification of analytes in umbilical cord plasma samples is < 0.72 ng/mL and 0.92 ng/g in placental tissue samples. The relative deviation of this method was < 15% for intra- and inter-day assays, and the accuracy ranged between 88 and 105%. The extraction recovery of the four analytes ranged between 89 and 96% in umbilical cord plasma, and 64 and 80% in placental tissue. No significant matrix effect was observed in the presented method.

This report describes the development and validation of an LC-MS/MS method for the quantitative determination of glyburide (GLB), its five metabolites (M1, M2a, M2b, M3, and M4) and metformin (MET) in plasma and urine of pregnant patients under treatment with a combination of the two medications. The extraction recovery of the analytes from plasma samples ranged between 87% and 99%, and 85%–95% for urine samples. The differences in retention times among the analytes, and the wide range of the concentrations of the medications and their metabolites in plasma and urine patient samples required the development of three LC methods. The lower limit of quantitation (LLOQ) of the analytes in plasma samples was as follows: GLB, 1.02 ng/mL; its five metabolites, 0.100–0.113 ng/mL and 4.95 ng/mL for MET. LLOQ in urine samples was 0.0594 ng/mL for GLB, 0.984–1.02 ng/mL for its five metabolites and 30.0 μg/mL for MET. The relative deviation of this method was < 14% for intra-day and inter-day assays in plasma and urine samples, and the accuracy ranged between 86% and 114% in plasma, and 94% to 105% in urine. The method described in this report was successfully utilized for determining the concentrations of the two medications in patient plasma and urine.

Recent in vitro data obtained in our laboratory revealed similarities between baboons and humans in the biotransformation of bupropion (BUP) by both hepatic and placental microsomes. These data supported the use of baboons to study BUP biotransformation during pregnancy. The aim of this investigation was to determine the pharmacokinetics of BUP in baboons during pregnancy and postpartum, as well as fetal exposure to the drug after intravenous administration. Pregnant baboons (n = 5) received a single intravenous bolus dose of bupropion hydrochloride (1 mg/kg) at gestational ages 94-108 days (midpregnancy), 142-156 days (late pregnancy), and 6 weeks postpartum. Blood and urine samples were collected for 12 and 24 hours, respectively. The concentrations of BUP, hydroxybupropion (OH-BUP), threohydrobupropion, and erythrohydrobupropion in plasma were determined by liquid chromatography-tandem mass spectrometry. Relative to the postpartum period, the average midpregnancy clearance of BUP trended higher (3.6 6 0.15 versus 2.7 6 0.28 l/h per kg) and the average C max (294 6 91 versus 361 6 64 ng/ml) and the area under the curve (AUC) of BUP values (288 6 22 versus 382 6 42 h·ng/ml) trended lower. AUC OH-BUP also tended to be lower midpregnancy compared with postpartum (194 6 76 versus 353 6 165 h·ng/ml). Whereas the observed trend toward increased clearance of BUP during baboon pregnancy could be associated with a pregnancy-induced increase in its biotransformation, the trend toward increased renal elimination of OH-BUP may overshadow any corresponding change in the hydroxylation activity of CYP2B.

This report describes the development and validation of a chromatography/tandem mass spectrometry method for the quantitative determination of pravastatin and its metabolite (3α-hydroxy pravastatin) in plasma and urine of pregnant patients under treatment with pravastatin, as part of a clinical trial. The method includes a one-step sample preparation by liquid-liquid extraction. The extraction recovery of the analytes ranged between 93.8% and 99.5% in plasma. The lower limits of quantitation (LLOQ) of the analytes in plasma samples were 0.106 ng/mL for pravastatin and 0.105 ng/mL for 3α-hydroxy pravastatin; while in urine samples they were 19.7 ng/mL for pravastatin and 2.00 ng/mL for 3α-hydroxy pravastatin. The relative deviation of this method was < 10 % for intra-day and inter-day assays in plasma and urine samples, and the accuracy ranged between 97.2% and 106% in plasma, and 98.2% to 105% in urine. The method described in this report was successfully utilized for determining the pharmacokinetics (PK) of pravastatin in pregnant patients enrolled in a pilot clinical trial for prevention of preeclampsia.