Development and Validation of UPLC Tandem Mass Spectrometry Assay for Ceftibuten and Sulbactam in Human Plasma.

A sensitive and rapid ultra-performance liquid chromatography coupled with -tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine ceftibuten (CTB) and sulbactam (SUL) in human plasma. An ACQUITY UPLC HSS T3 C18 (2.1 × 100 mm), 1.8 µm column with gradient elution of water (0.1% formic acid) and acetonitrile was used for separation at a flow rate of 0.2 mL/min. This method involves a simple sample preparation with acetonitrile. The calibration curves of CTB and SUL in plasma showed good linearity over the concentration range of 0.50-25 µg/mL and with a correlation coefficient (r2) >0.99. This method was validated in terms of selectivity, linearity, precision, accuracy and stability. High precision was obtained with coefficients of variation <15%. Excellent recovery in the range of 90-104% was achieved for CTB and SUL was 86-110%. The method has the potential utility to support pharmacometric modeling in clinical practice and biopharmaceutic studies.

Urinary phthalate metabolite and BPA concentrations in women with cervical cancer.

Environmental pollutants are involved in the development and progression of numerous cancers, including cervical cancer (CC). One possible explanation for this is the ability of several pollutants to mimic natural hormones. This study aimed to evaluate the urinary concentrations of monoesters of phthalates and bisphenol A (BPA) in women with CC. A total of 45 women were included: 15 in the control group, 12 with CC diagnosis classified in early stages IA-IIB, and 18 in late stages III-IV. Urine samples were analyzed for BPA, mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono 2-ethylhexyl phthalate (MEHP) using high-performance liquid chromatography coupled to a tandem mass detector. The detection rate of environmental pollutants was 100%, with a median concentration in the control group and early-, and late-stage groups of 10.4, 9.2, 4.3, 38.4, and 12.9 µg L-1; 3.1, 3.1, 151.1, 54.5, and 30.4 µg L-1 and 1.9, 92.8, 3.6, 31.0, and 9.3 µg L-1 for BPA, MEHP, MBzP, MBP, and MiBP, respectively This study reveals high levels of phthalates, particularly MEHP, in urine samples of women with CC associated with human papillomavirus (HPV) infection. Further studies are needed to evaluate the possible role of phthalates in synergy with HPV in progression to CC.

Simultaneous determination of four serotonin selective reuptake inhibitors by an UPLC MS-MS method with clinical application in therapeutic drug monitoring.

An analytical method of ultra-high performance liquid chromatography coupled to tandem mass spectrometry detection was developed and validated for the simultaneous quantification in plasma of four selective serotonin reuptake inhibitor antidepressants: sertraline, escitalopram, paroxetine, fluoxetine, and its metabolite norfluoxetine. A simple protein precipitation was performed with acetonitrile containing 100 ng/mL of indomethacin, which was used as internal standard. Chromatographic separation was carried out on an Acquity BEH C18 column with isocratic elution of the mobile phase consisting of 5 mmol/L ammonium acetate with 0.1% formic acid (A) and acetonitrile (B) at a 60:40 proportion, respectively. The flow rate was 0.4 mL/min with a run time of 5 min. A positive electrospray ionization source was used for detection. The method was linear in a range of 5-800 ng/mL, with determination coefficients greater than 0.991. The accuracy ranged from 91% to 112% for intra-assay and from 89% to 112% for inter-assay. The variation coefficients ranged from 3.1% to 14.88% for intra-assay and from 3.60% to 14.74% for inter-assay precision. The method was successfully applied for the analysis of 73 samples from patients under treatment with these antidepressants; 36.9% of the samples had concentrations outside therapeutic ranges. This method can be applied for routine analysis in clinical practice, simplifying sample processing, reducing analysis time and consequently the costs associated with it.

Environmental endocrine disruptor concentrations in urine samples from Mexican Indigenous women.

The Indigenous communities in Mexico show significant degrees of vulnerability to pollution due to the lack of knowledge of health risks, traditions, low levels of support, and restricted access to healthcare. As a result, exposure to environmental endocrine disruptors increases in these populations through plastic components or indoor air pollution. Therefore, the aim of the study was to evaluate the exposure to phthalate metabolites, 1-hydroxypyrene, and bisphenol A through biomonitoring data from indigenous Mexican women. A total of 45 women from the Tocoy community in San Luis Potosí, Mexico, were included. Urine samples were analyzed for Bisphenol A and 4 phthalate metabolites by ultra-performance liquid chromatography couples to tandem mass spectrometry; additionally, the 1-hydroxypyrene concentrations were evaluated by high-performance liquid chromatography coupled to a fluorescence detector. Among the main pollution sources were the use of plastic containers and burning garbage (98-100%). Indigenous women presented an exposure of 100% to mono-2-ethyl phthalate, mono-n-butyl phthalate, and 1-hydroxypyrene, with a median (25th-75th percentiles) of 17,478 (11,362-37,355), 113.8 (61.7-203.5), and 1.2 (0.9-1.7) µg/g creatinine, respectively. The major findings show urinary mono-2-ethyl phthalate concentrations higher than those measured from other studies. Therefore, these results show an impressive exposure to di(2-ethylhexyl) phthalate in Indigenous women. The current study reflects the absence of regulatory policies in marginalized populations. It highlights the need to design strategies that mitigate exposure and the importance of biological monitoring to evaluate and prevent health risk associated with exposure to environmental endocrine disruptors.

Factors associated with fluoxetine and norfluoxetine plasma concentrations and clinical response in Mexican patients with mental disorders.

Over the last few years, fluoxetine has been one of the most prescribed medications for the treatment of diverse psychiatric conditions in Mexico. Fluoxetine therapeutic effect is consequence of the joint action of the parent drug and its active metabolite, norfluoxetine. However, the clinical efficacy of fluoxetine, can be affected due to diverse factors, such as drug-drug interactions and the large interindividual variability in the pharmacokinetics of this drug. The aim of this study was to determine the factors associated with variability in plasma concentrations of fluoxetine and norfluoxetine and its association with the therapeutic response. Fluoxetine and norfluoxetine plasma concentrations were quantified by liquid chromatography in 81 Mexican patients with mental disorders; 25% of the patients had no medication adherence and 40% were below the reference range of fluoxetine plus norfluoxetine plasma concentrations. The results showed that concentrations can be affected by fluoxetine metabolism caused by CYP2D6 phenotype and the concomitant administration of olanzapine. Furthermore, CYP3A5 and CYP2C19 phenotype were associated with lower anxiety and depression control during treatment with fluoxetine. This study can be a starting point to elucidate the causes of fluoxetine variable response in Mexican patients with mental disorders, as well as to detect and support medication adherence.