An LC-ESI-MS/MS assay for the therapeutic drug monitoring of 15 antiseizure medications in plasma of children with epilepsy.

Oral antiseizure medications are the preferred option for the clinical treatment of epilepsy. Therapeutic drug monitoring has become an important means of achieving individualized treatment of epilepsy. A sensitive, accurate and rapid LC-ESI-MS/MS method was developed and validated for the simultaneous determination of 15 antiseizure medications in human plasma (carbamazepine, gabapentin, pregabalin, phenytoin, zonisamide, oxcarbazepine, tiagabine, lamotrigine, topiramate, phenobarbital, lacosamide, primidone, 10,11-Dihydro-10-hydroxy carbamazepine, ethosuximide, and levetiracetam). The sample preparation procedure was an one-step protein precipitation with methanol. Mass detection was performed in ionization polarity switching mode (positive-negative-positive) using multiple reaction monitoring mode. A "boot-shaped" gradient elution program was applied to separate and concentrate those target analytes, resulting in symmetrical peak shapes within 10 min, without endogenous interference. The method showed great linearity over the concentration ranges with acceptable correlation coefficients (0.9966-0.9996). The precision and accuracy values for intra- and inter-assays were within ±15%. Consequently, the method was successfully implemented on pediatric patients undergoing mono- or polytherapy for epilepsy and provided timely concentration results to ordering clinicians.

Appropriate indicated use for IVIG in neonatal infections / Uso indicado y apropiado de la inmunoglobulina G intravenosa para el tratamiento de infecciones neonatales

Infection is a leading cause of mortality and morbidity in the newborn and preterm neonates due to immuno-incompetence in these patients. Administration of intravenous immunoglobulin (IVIG) provides immunoglobulin G (IgG) that can protect the body from infection. In theory, morbidity and mortality due to infections in newborns and preterm infants could be reduced by the administration of IVIG. Two meta-analyses were evaluated comparing IVIG to treat various infection versus conventional treatments. The results showed that IVIG is not effective as an adjunctive treatment for suspected or proven infections in neonates.

La infección es la causa principal de la mortalidad y de la morbilidad entre los recién nacidos y los neonatos prematuros debido a la incompetencia inmunológica de estos pacientes. El suministro de inmunoglobulina por vía intravenosa brinda la inmunoglobulina G que protege al cuerpo humano de las infecciones. En términos teóricos, la morbilidad y la mortalidad por infecciones en recién nacidos y en bebés prematuros, podrían reducirse si se administra inmunoglobulina G intravenosa. Se evaluaron dos meta-análisis que comparaban el uso de la inmunoglobulina G intravenosa para tratar diversas infecciones con los tratamientos convencionales. Los resultados demostraron que dicha inmunoglobulina no es eficaz como tratamiento adyuvante para combatir sospechas de infección o infecciones comprobadas en los recién nacidos.

Part IV: Design, synthesis and antitumor activity of fluoroquinolone C-3 heterocycles: bis-oxadiazole methylsulfide derivatives derived from ciprofloxacin.

To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate, oxadiazole thiol (5), which was further modified to the bis-oxadiazole methylsulfides (7a-7h) and the corresponding dimethylpiperazinium iodides (8a-8h), respectively. Structures were characterized by elemental analysis and spectra data, and their anticancer activities in vitro against CHO, HL60 and L1210 cancer cells were also evaluated by MTT assay. The preliminary results show that piperazinium compounds (8) possess more potent activity than that of corresponding free bases (7).

[Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin].

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.