Building on recent breakthroughs in the field of microfluidic-based capture of rare cancer cells circulating in the blood, the present article reports on the use of Herceptin functionalized PDMS devices designed to efficiently capture from blood cancer cells, overexpressing the tyrosine kinase human epidermal growth factor receptor (HER2). The identification of patients overexpressing HER2 is critical as it typically associates with an aggressive disease course in breast cancer and poor prognosis. Importantly, HER2 positive patients have been found to significantly benefit from Herceptin (Trastuzumab), a humanized monoclonal antibody (MAb) against HER2. Disposable PDMS devices prepared using standard soft lithography were functionalized by the plasma polymerization of an epoxy-containing monomer. The epoxy-rich thin film (AGEpp) thus created could be conjugated with Herceptin either directly or through a polyethylene glycol interlayer. The properties and reactivity toward the monoclonal antibody conjugation of these coatings were determined using x-ray photoelectron spectroscopy; direct conjugation provided a good compromise in reactivity and resistance to biologically nonspecific fouling and was selected. Using the breast cancer cell line SK-BR-3 as a model for cells overexpressing HER2, the immunocapture efficacy of the Herceptin functionalized PDMS was demonstrated in model studies. Validation studies confirmed the ability of the device to efficiently capture (∼80% capture yield) HER2 positive cells from full blood.

IntroductionRosuvastatin reduces concentrations of total cholesterol (TC) and is used for the management of hypercholesterolemia and prevention of acute coronary syndromes. There are no published reports estimating infant exposure to rosuvastatin through breast milk.PurposeThe aims of this study were to quantify concentrations of rosuvastatin in human milk and plasma from a lactating woman taking rosuvastatin and to investigate potential infant exposure.Materials and methodsA 38-year-old breastfeeding mother was commenced on rosuvastatin 20 mg daily for secondary prevention of an acute coronary syndrome. Eight maternal breast milk samples and a single plasma sample were collected over a 24-hour period. The samples were quantified using a sensitive liquid chromatography–mass spectrometry (LC-MS/MS) method.ResultsThe average concentration of rosuvastatin in breast milk was 30.84 ng/mL, and a peak concentration of 58.59 ng/mL occurred at 17 hours after oral administration. Although the milk-to-plasma (M/P) ratio was 16.49 at 14 hours, the theoretical infant dosage (TID) and relative infant dose (RID) were 0.005 mg/kg/day and 1.50%, respectively.ConclusionThe findings suggest that only small amounts of rosuvastatin pass into breast milk. Should the maternal condition necessitate treatment, consideration could be given to the use of rosuvastatin during breastfeeding provided the infant is monitored.

A new validated analytical method for atenolol in plasma and milk was developed.

Atenolol use during breastfeeding should be undertaken with some precaution. If clinically indicated, an alternate beta blocker may be preferred.

A first of its kind, simple, rapid, and sensitive liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated for quantification of perindopril and perindoprilat in both human plasma and breast milk. The analytes and internal standards (phenazone and acetyl salicylic acid) were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column was used to provide an appropriate chromatographic separation of the analytes, followed by detection with tandem mass spectrometry. Gradient chromatographic and mass spectrometric detection conditions with mobile phases (A: 5% methanol + 0.1% formic acid in water v/v, and B: 95% methanol + 0.1% formic acid in water v/v) were developed to achieve a LOQ of 0.5 ng/mL in both human plasma and milk. The method was suitable of evaluating clinical samples. The mass transition was followed as m/z 369.10/172.00 for perindopril, m/z 339.00/168.10 for perindoprilat, m/z 188.90/55.95 for phenazone, and m/z 179.04/137.02 for acetyl salicylic acid. The developed method was optimized and validated with a linear range of 0.1-200 ng/mL (r = better than 0.99 for both perindopril and perindoprilat). The precision and accuracy values were within 15% CV. The overall recovery of the analytes was 80-110%. The method has good specificity and repeatability. Stability studies were conducted in both human plasma and bovine milk for up to 3 months, at the storage conditions of 25, 4, and -80 °C.