Widening the applications of the Just-Dip-It approach: a solid contact screen-printed ion-selective electrode for the real-time assessment of pharmaceutical dissolution testing in comparison to off-line HPLC analysis.

Over past years, the field of pharmaceutical dissolution testing has significantly expanded to cover not only the quality control of dosage forms, but also to play an important role in the bioavailability testing paradigm and screening of most formulations. These tests usually need a very long time sampling and monitoring, so that the automation of sampling is laborsaving. Problems often occur with these automatic devices due to sampling lines that may disconnect, crimp, carry over, become mixed up, or are inadequately cleaned. Potentiometric sensors, such as liquid contact (LC-ISE) or solid contact ion-selective electrodes (SC-SP-ISE), can provide timely data to be used for the real-time tracking of the amount of active pharmaceutical ingredients (APIs) released in the dissolution medium without these problems. In this work, we adopted the Just-Dip-It approach as a process analytical technology solution with the ultimate goal of advancing the ion selective sensors to their most effective use in pharmaceutical analysis. Two sensors were fabricated, the traditional LC-ISE and SC-SP-ISE. The sensing poly-vinyl chloride membranes of two electrodes were prepared using 2-nitrophenyl octyl ether as a plasticizer to soften the membrane, and the reduction in resistance to pioglitazone ions (PIO) permeability was achieved through the incorporation of sodium tetraphenylborate and calix[8]arene as a cationic exchanger salt and inclusion complexing ligand, respectively. Finally, prepared membranes were turned into the flexible perm-selective slices of hydrophobic plastic, which work as a barrier to other compounds, except for the PIO cation in the concentration range of 1 × 10-6 to 1 × 10-2 M and 1 × 10-5 to 1 × 10-2 M for SC-SP-ISE and LC-ISE, respectively. The challenges and opportunities of both sensors in comparison to a developed HPLC method were discussed for the dissolution testing of the combination dosage forms of pioglitazone. Potentiometric methods were validated according to IUPAC guidelines, while HPLC was validated according to ICH guidelines to ensure accuracy and precision.

Surface enhanced infrared absorption spectroscopy (SEIRA) as a green analytical chemistry approach: Coating of recycled aluminum TLC sheets with citrate capped silver nanoparticles for chemometric quantitative analysis of ternary mixtures as a green alternative to the traditional methods.

The past two decades have seen the full expansion of all fields of Nanotechnology, Chemometrics, Recycling, and Vibration spectroscopy into most of the research areas. The proposed method involves the harmonization of the previously mentioned fields as a vital tool to fulfill the concepts of sustainability and green analytical chemistry. This may reduce the negative impact of analytical laboratory activities on the surrounding environment and enables the implementation of sustainable development principles to analytical laboratories. This work compares the performance of surface enhanced infrared spectroscopy (SEIRA) with traditional chromatographic techniques for quantification of active pharmaceutical ingredients concerning the twelve principles of green analytical chemistry. The used aluminum TLC slides were recycled to be used as a SEIRA substrate. Citrate capped silver nanoparticles were synthesized via one step chemical reduction method, characterized, and deposited on the surface of the recycled aluminum TLC slides to be used as an active mid-infrared surface for quantification of the active pharmaceutical ingredient's combinations. SEIRA coupled with PLSR chemometric tool was developed, validated and successfully applied to mixtures having diverged concentration ranges (5, 30 and 500 µg ml-1) of Pholcodine, Pseudoephedrine and Paracetamol, respectively. Pholcodine is a synthetic or semi-synthetic opium alkaloid that derived from morphine. Pseudoephedrine is a sympathomimetic agent that is prohibited in sports competitions by the world antidoping agency at certain concentration levels. Paracetamol has analgesic and antipyretic actions. After optimization of the method parameters and number of latent factors, a good linear calibration model of the PLSR strategy was obtained as indicated by the lowest root mean square error of calibration and prediction obtained and the regression coefficients R2 of 0.9912, 0.9888, and 0.9992, respectively. The calibration ranges for the three drugs in their pharmaceutical combinations was 2.5-12.5, 15-75 and 200-600 µg ml-1, respectively. The method showed high resolving power for the three drugs in presence of excipients and good recoveries were obtained in a range of 97-102% with relative standard deviation < 2. The developed lab on a chip SEIRA analyzer in comparison to the traditional chromatographic techniques does not only fulfill the twelve principles of GAC but also it combines the merits of high throughput straightforward fingerprint analyzers, portable to measure samples on its place, cost effective, reduced sample volume and solvent consumption, coupled with intelligent chemometric tools to analyze multiple samples, reduced trials and time to get results.

Determination of pioglitazone, its metabolite and alogliptin in human plasma by a novel LC-MS/MS method; application to a pharmacokinetic study.

A novel, high throughput and sensitive LC-MS/MS assay method was developed and fully validated for quantitative determination of pioglitazone, its hydroxyl metabolite and alogliptin in human plasma. A simple and rapid sample preparation procedure based on protein precipitation technique with acetonitrile was utilized. Chromatographic separation was achieved on C8 (50 × 4.6 mm, 5 µm) Kinetex® analytical column using methanol and 0.1% formic acid in a gradient elution mode at a flow rate of 0.7 mL/min with injection volume of 8 µL. Detection was performed on a triple quadrupole mass spectrometer accompanied with electrospray ionization (ESI) technique in positive mode, operating in multiple reaction monitoring, with the transitions of 357.2 → 119.1, 373.1 → 150.1, 340.3 → 116.1, 361.1 → 138.1 and 343.2 → 116.1 m/z for pioglitazone, its hydroxyl metabolite, alogliptin, pioglitazone-d4 (IS-1) and alogliptin-d3 (IS-2), in order. Analysis was achieved within 4 min over a linear concentration range of 10-3000 ng/mL, 5-2000 ng/mL and 3-300 ng/mL, for pioglitazone, hydroxyl pioglitazone and alogliptin, in order. The method was fully validated according to FDA guidelines. The developed method was used for estimation of the three studied analytes in human plasma and pharmacokinetic parameters were demonstrated after oral dose administration of Oseni® tablets to Egyptian healthy volunteers.

Undifferentiated Endometrial Carcinoma, an Immunohistochemical Study Including PD-L1 Testing of a Series of Cases From a Single Cancer Center.

Undifferentiated endometrial carcinoma (UEC) is a rare and poorly recognized entity, associated with a poor outcome. The clinical, pathologic, and immunohistochemical features of 17 cases diagnosed at our center are described. The median age was 60 yr. Postmenopausal bleeding was the most common presenting symptom (76.9%). Most patients presented with advanced stage (64.7%). Total hysterectomy with bilateral salpingo-oophorectomy was the commonly offered surgical treatment (80.0%). Nine (52.9%) patients received adjuvant treatment. The median overall survival was 11 mo. Pure UEC was seen in 8 cases (47.0%), while dedifferentiated carcinoma in 5 cases (29.4%). The epithelial component was part of carcinosarcoma or was mixed with serous carcinoma in 2 cases (11.8%) each. Positivity for one or more of the cytokeratin cocktails, mostly as strong focal staining, was evident in 16 cases (94.1%). PAX-8 was negative in 13 cases (86.7%). BRG-1/SMARCA4 was lost in 3 cases (20.0%). Eleven cases (64.7%) were MLH1/PMS2 deficient. Ten cases (66.7%) were positive for programmed death ligand 1, with positivity in 10%, 20%, and 100% of tumor cells detected in a single case each. Only 2 of 11 (18.2%) referral cases were correctly diagnosed as UEC. UEC is a rare tumor that is frequently misdiagnosed. A panel of immunostains is necessary to make the correct diagnosis. The range of positivity for programmed death ligand 1 testing suggests that immunotherapy might be considered in the adjuvant setting, especially with the poor response of this tumor to traditional therapies.

Prevalence of Abnormal Pap Smears: A Descriptive Study from a Cancer Center in a Low-Prevalence Community

Background and aims: Cervical cancer is the fourth most common cancer in women worldwide and the 13th in Jordan. The cervical smear (Pap smear) is a simple approach to detect pre-cancerous cervical lesions. The aim of this study was to evaluate the prevalence of abnormal cervical smears in women seen at the Early Detection/Community Outreach clinic of King Hussein Cancer Center (KHCC). Materials and Methods: In this retrospective study, reports of routine cervical Pap smears performed in the pathology department at KHCC from January 2007 to December 2016, were reviewed. During this period, a total of 5,529 routine smears were assessed for epithelial abnormalities and histopathological grading. Results: A total of 210 (3.8%) abnormal Pap smears were found, with atypical squamous cell of undetermined significance (ASC-US) reported in 110 (52.4%) cases, atypical glandular cells of undermined significance (AGUS) in 58 (27.6%), low grade squamous intra-epithelial lesion (LSIL) in 27 (12.9%) and high grade intra-epithelial lesion (HSIL) in 13 (6.2%). Only single cases of ASC-H and squamous cell carcinoma were reported. The available biopsies showed benign findings in 70.1% of cases, low grade squamous intraepithelial lesions in 11.5% and high grade squamous intraepithelial lesions in 18.4%. Conclusions: The low epithelial cell abnormality (EPCA) prevalence illustrated in this study argues against introduction of population-based HPV testing and vaccination. It calls for a more cost-effective measures in a country with limited resources, where a more widely available Pap-smear testing might suffice.

Ovarian transposition before pelvic irradiation: indications and functional outcome.

AIM: To investigate the indications and effectiveness of ovarian transposition before pelvic irradiation. METHODS: This was a retrospective analysis of patients with malignancies who underwent ovarian transposition before pelvic irradiation. The collected data included age of patient, type and stage of cancer, details of irradiation treatment, and clinical and biochemical parameters of ovarian function during the period of follow-up. RESULTS: Fourteen adult and four pediatric patients with different types of cancers underwent ovarian transposition during the study period. The common tumor types for the adult patients were cervical cancer (n = 4), rectal cancer (n = 4) and medulloblastoma (n = 3), and for pediatric patients was medulloblastoma (n = 2). The mean age for adult patients was 31 years (range, 21-40) and for pediatric patients was 7 years (range, 4-10). Of the adult patients, 10 had adjuvant chemotherapy and four had neoadjuvant chemotherapy added to their radiotherapy program. All pediatric patients received adjuvant chemotherapy. Thirteen of 14 (92.85%) adult patients had normal serum level of follicle-stimulating hormone (FSH; ≤12 IU/L) and E2 (>50 pg/mL). Only one patient had premature menopause. All pediatric patients demonstrated a normal serum level of FSH (<12) and E2 for their age at 3 and 6 months after completion of their treatment. The mean follow-up was 42 months (range, 34-50). CONCLUSION: Ovarian transposition is an effective procedure for the preservation of ovarian function. Young patients with non-hormone-dependent pelvic tumors should be offered a laparoscopic ovarian transposition before the start of pelvic radiotherapy.

Management of cancer during pregnancy: obstetric and neonatal outcomes.

OBJECTIVE: This study aimed to assess the management and the obstetric and neonatal outcomes of pregnancies complicated by cancer. METHODS: A retrospective analysis of patients with cancer during pregnancy who were treated at King Hussein Cancer Center and King Abdullah University Hospital in Jordan between January 2002 and December 2009 was conducted. The medical records of patients with invasive cancer diagnosed during pregnancy and their newborns were reviewed to retrieve information on treatment and obstetric and neonatal outcomes. Numerical data were tested for normal distribution using Kolmogorov-Smirnov. Statistical analyses were conducted using SPSS 18.0. RESULTS: A total of 46 patients with a diagnosis of cancer in pregnancy were treated. The most common tumor types were breast cancer, hematologic malignancies, and gastrointestinal malignancies. In 17 patients, a miscarriage or a termination of pregnancy occurred in the first trimester. In 25 of 46 patients, a single or a combination of treatment modalities was commenced. The distribution of therapies was as follows: chemotherapy alone, n = 5; surgery alone, n = 7; surgery and chemotherapy, n = 6; surgery and radiation therapy, n = 1; surgery with chemotherapy and radiation therapy, n = 3; chemotherapy and radiation therapy, n = 1; interferon, n = 1; and hormonal therapy, n = 1. The mean (SD) gestational age at delivery was 35.7 (2.7) weeks. The mean birth weight was 2580 (870) g. Preterm delivery occurred in 17 patients. There were 4 neonatal deaths, 2 of them delivered at 33 weeks, 1 delivered at 34 weeks, and 1 delivered at 35 weeks gestation. There were no congenital malformations. CONCLUSIONS: The remarkable finding is a high rate of iatrogenic preterm delivery with a high rate of neonatal mortality. Delivery should be postponed preferably until after a gestational age of 35 weeks.