HPLC-MS/MS method for determination of betamethasone in human plasma with application to a dichorionic twin pregnancy pharmacokinetic and placental transfers studies

Abstract Betamethasone (BET) is a synthetic glucocorticoid recommended for pregnant women at imminent risk of preterm birth before 34 weeks to reduce neonatal complications. There are different techniques to describe BET plasma quantification. However, none quantified the plasmatic concentration of BET in dichorionic (DC) twin pregnancies using LC-MS. Our objectives were to develop and validate a method for quantifying BET by LC-MS for pharmacokinetic (PK) and placental transfer studies in DC twin pregnancies. Blood samples were collected after intramuscular administration of a single BET dose containing 6 mg disodium phosphate + 6 mg acetate. BET was determined in plasma by liquid-liquid extraction. The method showed linearity in the range of 2-250 ng/mL, as well as precision and accuracy with a coefficient of variation and relative standard errors ≤ 15%. Additionally, the method presented selectivity and did not present matrix or carry-over effect. Stability tests also presented coefficient of variation and relative standard errors ≤ 15%. This is the first study which describe maternal and fetal plasma concentrations of BET in a DC twin pregnancy. The BET PK parameters were AUC0-∞, CL/F, Vd/F, Cmax, Tmax of 292.20 h*ng/mL, 39.08 L/h, 278.72 L, 25.55 ng/mL and 0.58 h, respectively. The placental transfer ratios of umbilical vein/maternal vein and intervillous space/maternal vein were 0.14 and 0.19 and 0.40 and 0.27 for both twins, respectively. However, a clinical study with more subjects is imperative to confirm this higher concentration of BET in the intervillous space

Therapeutic drug monitoring of gabapentin: the applicability in patients with neuropathic pain

Abstract Gabapentin is an antiepileptic drug prescribed for several neuropathic pain conditions. This study aimed to evaluate gabapentin (GAB) trough plasma concentration range and the applicability of therapeutic drug monitoring in patients with neuropathic pain. Fifty-three patients with neuropathic pain, aged 20 to 75, received gabapentin as treatment for at least 7 days. Gabapentin plasma concentration was sampled before GAB administration and quantified by liquid chromatography with a UV detector. GAB trough plasma concentration ranged between 0.40 and 11.94 µg/mL in patients with chronic neuropathic pain. No differences were observed in terms of GAB plasma concentrations between responsive and non-responsive patients. Our data suggest that the reference ranges suggested in the literature for patients with epilepsy should not be used for patients with neuropathic pain. Therapeutic drug monitoring of GAB was shown to be an important tool to assess treatment adherence.

Simple and rapid HPLC-UV methods for gabapentin quantification in human plasma and urine: applicability in pharmacokinetics and drug monitoring

Aim: We aimed to develop methods to determine gabapentin (GAB) in biological samples using high-performance liquid chromatography (HPLC) with application in pharmacokinetics and therapeutic drug monitoring. Methods: Simple, rapid and efficient HPLC-UV methods to quantify GAB in human plasma and urine were developed and validated for clinical analysis of GAB. The 1-fluoro-2,4-dinitrobenzene (FDNB) was used as derivatization agent. For plasma samples, protein precipitation using acetonitrile was performed, before the derivatization reaction. Urine samples were cleaned-up by liquid-liquid extraction with dichloromethane:n-butanol (1:1, v/v) after derivatized. Amlodipine besilate was used as internal standard (IS). Results: Gabapentin and IS were resolved on LiChrospher® C18 RP column and a mixture of 50 mM sodium phosphate buffer (pH 3.9):methanol (27:73, v/v) as mobile phase, at 1.2 mL/min. The methods used small sample volumes, 100 and 50 µL of plasma and urine, respectively. Linearity was obtained in the interval of 0.2-14 µg/mL in plasma and 2-120 µg/mL in urine. Both methods showed to be selective, without carry-over effect, precise, accurate and stable in different conditions. GAB plasma concentration in patients receiving 600 to 3600 mg/day of GAB ranged between 0.40 to 11.94 µg/mL at steady-state. Conclusions: The methods described in this study were simple, rapid and fulfill all validation requirements. They were easily and successfully applied for population pharmacokinetics and therapeutic drug monitoring of GAB in patients with chronic pain.

Analysis of extemporaneous oral liquid from commercially available drugs in hospital

ABSTRACT The objective of this study was to identify drugs that received dose adjustments (DA) and pharmaceutical alternatives (PA) that avoid DA, and calculate the economic percentage of this replacement. A descriptive, observational and cross-sectional study was performed in a second level hospital. The pharmacy and nursing services was accompanied to identify the drugs that received DA and the compounding techniques. After identifying all the drugs that received DA, was identified in the Brazilian market the corresponding pharmaceutical alternative, with the Drugs Price List of Brazilian Health Regulatory Agency. For those drugs that was not available any PA, was performed a research of studies that describe compounding techniques in international scientific databases. Was identify 88 drugs that received DA, and these, 50 do not have any PA. Were identified compounding techniques to 40 drugs. Although any drug has your own particularity of compounding, the compounding techniques can be grouped in five categories. The standardization of 29 drugs can reduce in 28% the DA procedure and cost saving of 34,85%/month. We can conclude that every three drugs prescribed, one received DA and every three DA, one can be avoided by the selection of 29 PA, saving cost as well. The use and standardization of five techniques would attend the pharmaceutics recommendations for better dissolution, bioavailability and patient safety.