The path to the scientific definition of drugs took advantage of advances in systematic botany, which Linnaeus put a full stop to in the eighteenth century, and in chemistry, which, following the seventeenth-century boost from Paracelsus, reached its peak in the following century.
Paracelsus (Philipp Theophrast Bombast von Hohenheim 1493-1541) rejected ancient medical theory, still in vogue, of diseases as imbalances of the four humours governing the body, i.e. blood, phlegm, yellow bile and black bile and, along with that, he rejected Galen’s associated remedies. He publicly burned Avicenna’s Canon of Medicine.
In his Renaissance vision, man is part of nature, the microcosm connected to the macrocosm of the universe, whose forces should be investigated with magical-alchemical means, to explore the connections and discover its quintessence. In this vision, astral influence, on the one hand, and matter in its essential components, on the other, became fundamental, even in illnesses – Paracelsus identified this in metals (salt, lead and mercury).
In the pharmacological field, Paracelsus’ legacy was a jolt to Galen’s dogma and a veering towards iatrochemistry "that is, the therapeutic use of chemicals" (Ragazzi 2000 pp. 7-8) or spagyric, "from the Greek ‘spao’ and ‘aghiero’, i.e. divide and join… the new therapeutic approach, based first of all on the analysis of the bodies… and then on their combination" (ibid), that is, the two-way chemical process of analysis and synthesis. Chemical operation found successfully practical applications, its origin was studied scientifically and chemistry became a discipline in the eighteenth century. The first chair of pharmaceutical chemistry was established in Montpellier in 1675.

The clear affirmation of spagyric can be found in Pharmacopoeia medico-chymica by the German physician Johann Schröder (1600-1664), who discovered arsenic, published in 1641. Widely read, it is held at the Library of Pharmaceutical and Pharmacological Sciences of the University of Padova in a 1688 edition annotated by Michael Ettmüller (1644-1683) (digital copy). The work discusses the three types of simples: plant, animal and mineral. In explicit homage to Paracelsus, it explores the qualities of the vegetable simples according to not only tradition, "caliditate, frigiditate &c." (p. 1), but also according to other, hidden qualities, "aliis occultis" (ibid), determined by their chemical composition, "determinandae sunt a mistura materiali seu textura minutissimarum particularum" (ibid). Hidden qualities can be manifested through taste and smell, released by the finer and more volatile particles, present in different percentages depending on the concentration of oil and salt. Metals can be distinguished based on the purity, determined by the consistency acquired when they are forming in the bowels of the earth, passing from liquid form to solid "per debitam fermentationem" (p. 229). This can be tested through their resistance to combustion. The purest metal is gold. Schröder refers to the theories of Paracelsus of the bond between microcosm and macrocosm, adopting it in the correspondence between the seven planets, metals and parts of the human body. Thus, the sun corresponds to gold and benefits the heart. The alchemical transmutation of metals, from mercury to gold, the "lapis philosophicum" is rejected (p. 230). The description of the simples is accompanied by details of the chemical operation to be performed in their preparation as medicines. The elements are indicated by alchemical symbols, derived from the astrological ones for metals, based on their correspondence with the planets.

Nicolas Lémery (1645-1715), combined the skills of a chemist and a pharmacist. He shifted chemistry towards a mechanistic vision, more linked to the corpuscular aspect than the alchemical one of Paracelsus, always subject to experimental verification. The Cours de Chymie and the Pharmacopee universelle became reference texts. In support of Pharmacopoee, Lémery published the Dictionnaire universel des drogues simples in 1698, an annotated list of drugs. The 1760 edition is held at the Library of Pharmaceutical and Pharmacological Sciences of the University of Padova (digital copy). The author emphasised the importance of correct identification of drugs to avoid errors, adulteration or abuse, sometimes driven by economic interests. In the foreword, with regards to mineral drugs, Lémery immediately denies the link between planets and diseased parts of the body, suggesting to look for causes, which are closer such as chemical composition: "Mais ce n'est pas dans les influënces planétaires qu'il faut aller chercher les vertus des metaux; nous voyon des causes bien plus prochaines... comme à la disposition de leurs parties" (p. xii). In the dictionary, however, chemistry barely appears, leaving Pharmacopee as the most widely used reference. The dictionary lists the drugs in alphabetical order, and records nomenclature, description, virtues and etymology. The description of the plant-based drugs is much more precise, in particular for the parts used in determination of the species. The range or distribution of the plants is described and the parts to be used in pharmacy. The synonyms used by different authors are compared. Therefore, for the chaste tree, we find listed Agnus Castus. Gesn. Hort. (Gessner), Salix amerina. Matth. (Mattioli), and Vitex foliis angustioribus cannabis modo dispositis C.B. Pit. Tournef. (Bauhin and Tournefort). The list is alphabetical, but plants are grouped by the same species. The drugs’ virtues are recorded in very terse terms: vomitiva, astringente, risolutiva, emetica, carminativa, digestiva, aperitiva, sudorifera, purgativa (vomiting, stringent, resolving, emetic, carminative, digestive, stimulating appetite, sudorific, purgative). Each dictionary entry closes with the etymology of the name, and summarises a characteristic of the drug: "Aquila ab acumine, id est celeritate volatus", Chelidonium, from the Greek word for swallow, because the bird uses it to restore sight to its young; Cardamine (dentaria in Italian) for the shape of the roots is similar to teeth (denti in Italian); Bittersweet for the taste of its roots; Grape hyacinth (muscari) for its musk fragrance, Persica for its geographic provenance. In the back of the book there are illustrations of the principle plant, animal and mineral drugs. The parts of the plants useful for identification of the species are identified – very briefly but schematically: the roots, stems, leaves and flowers. The lack of realism is especially evident for the animals (pl. XXV).