Environmentally Oriented Models and Methods for the Evaluation of Drug × Drug Interaction Effects

<div><p>This detailed review compares known and widely used methods for drug interaction estimation, some of which now have historical significance. Pharmaceutical application has been noted as far back as several thousand years ago. Relatively late in the 20th century, however, researchers became aware that their fate and metabolism, which still remain a great challenge for environmental analysts and risk assessors. For the patient's well-being, treatment based on the mixing of drugs has to be effective and should not cause any side effects (or side effects should not have a significant impact on health and mortality). Therefore, it is important to carefully examine drugs both individually and in combinations. It should be also stated that application form/way of entering the living organism is of great importance as well as the age and the place in the trophic system of the organism in order to eliminate harmful dosages in the case of infants’ accidental intoxication.</p></div

MS/MS spectrum of AML 2 with proposed structures of each fragment ion.

<p>MS/MS spectrum of AML 2 with proposed structures of each fragment ion.</p

Various physical-chemical properties of AML and its photodegradation products, and their estimated removal with sewage sludge based on QSAR (EPI Suite).

a<p>Octanol-water partition coefficient (criteria: log K_ow <1 highly soluble in water (hydrophilic);>4 not very soluble in water (hydrophobic)).</p>b<p>Soil organic carbon-water partitioning coefficient (criteria: log K_oc <1.5 negligible sorption to sludge, rapid migration to ground water; 1.5–2.4 low sorption to sludge, moderate migration to ground water; 2.5–3.4 moderate sorption to sludge, slow migration to ground water; 3.5–4.4 strong sorption to sludge, negligible to slow migration to ground water).</p><p>Various physical-chemical properties of AML and its photodegradation products, and their estimated removal with sewage sludge based on QSAR (EPI Suite).</p

MS/MS spectrum of AML 1 with proposed structures of each fragment ion.

<p>MS/MS spectrum of AML 1 with proposed structures of each fragment ion.</p

Degradation products of amlodipine identified during the irradiation of river water samples by xenon lamp light.

<p>Degradation products of amlodipine identified during the irradiation of river water samples by xenon lamp light.</p

Photodegradation rate constants (<i>k</i>) and half-lives (t_1/2) of AML in various matrices exposed to solar or xenon lamp irradiation.

<p>Photodegradation rate constants (<i>k</i>) and half-lives (t_1/2) of AML in various matrices exposed to solar or xenon lamp irradiation.</p

Kinetic curves for AML obtained for various conditions: exposure to xenon lamp irradiation (a) and exposure to natural sunlight including eight different matrices (b).

<p>Kinetic curves for AML obtained for various conditions: exposure to xenon lamp irradiation (a) and exposure to natural sunlight including eight different matrices (b).</p

Proposed photodegradation pathway of amlodipine.

<p>Proposed photodegradation pathway of amlodipine.</p

Phototransformation of Amlodipine: Degradation Kinetics and Identification of Its Photoproducts

<div><p>Nowadays, monitoring focuses on the primary compounds and does not include degradation products formed during various biological and chemical processes. Transformation products may have the same effects to human health and the environment or sometimes they can be more toxic than the parent compound. Unfortunately, knowledge about the formation of degradation products is still limited, however, can be very important for the environmental risk assessment. Firstly, the photodegradation kinetic of amlodipine was investigated in two experimental conditions: during the exposure to solar radiation and during the exposure to the light emitted by the xenon lamp. In all cases degradation of amlodipine followed a pseudo-first-order kinetics. In the next step, identification of transformation products of amlodipine formed during the exposure to xenon lamp irradiation was performed using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). As a result sixteen photoproducts were identified, their structures were elucidated and ultimately the transformation pathway was proposed. Fifteen compounds (out of 16 photoproducts) were newly identified and reported here for the first time; some of those compounds were formed from the first photoproduct, amlodipine pyridine derivative. Several analytes were formed only in acidic or basic conditions. Furthermore, the occurrence of amlodipine and its identified degradation products was investigated in environmental waters. Only one out of 16 compounds was found in wastewater effluent. The possibility of the sorption of examined analytes to sewage sludge particles was discussed based on QSAR.</p></div