Прошу помочь разобраться с заключениями СМЭ

[Alexlp]

18 часов назад, SParilov сказал:

Да дело серьезное, ЕГЭ и увлечение зомби рулит.

Отсутствие чувства юмора - лечится.

 

17 часов назад, ТМВ сказал:

поделиться ?... применением тайных знаний ?

Знания - общедоступные. Метаболизму и фармакокинетике никотина посвящено масса исследований. В Кларке только ссылки на первоисточники мелким кеглем занимают полную страницу формата А4...

Цитата

_{Disposition in the Body Nicotine is readily absorbed from the gastrointestinal
tract, the buccal mucosa, the respiratory tract and from intact skin; it is widely
distributed throughout the tissues. Nicotine undergoes first-pass metabolism when
administered orally, thus reducing its bioavailability. It is widely distributed, crossing
the placental barrier and it is also found in breast milk. It is metabolised by
oxidation via cytochrome P450 isozyme CYP2A6 to cotinine and nicotine-10-Noxide,
followed by further degradation to produce hydroxycotinine, norcotinine,
and a ring cleavage product. Approximately 5% is excreted unchanged in the urine
in 24 h and ~10% as cotinine; the excretion of unchanged drug is decreased if the
urine is alkaline.
Blood Concentration
In a group of 150 habitual smokers, nicotine concentrations in samples of
plasma withdrawn 2 min after smoking were in the range 0.003–0.063 mg/L
(mean, 0.019); corresponding cotinine concentrations ranged from 0.02–
0.26 mg/L (mean, 0.22) [Kogan et al. 1981].
Six smokers received a single dose of nicotine (1 mg nasal spray; average
dose absorbed 0.8 mg; range, 0.7–1.0) and 6 others smoked cigarettes (1 puff
per min for 10 min; average dose absorbed 4.4 mg; range, 1.5–3.2); all subjects
also received a 30min IV infusion of nicotine (average dose 5.1mg; range,
4.1–6.3) beginning 70 min after administration of the spray or
commencement of smoking. In the subjects who received cigarettes, a
mean peak plasma concentration of 0.0398mg/L was attained at 8.2min in
arterial blood and 0.0186 mg/L at 11.9min in venous blood. In the subjects
who received nicotine intranasally, these values were 0.0104 mg/L in 4.7min
in arterial blood and 0.0054mg/L in 24.8min in venous blood. Mean peak
plasma concentrations in arterial and venous blood after the IV infusion
were 0.049mg/L in 29 min and 0.0295mg/L in 30 min, respectively [Gourlay,
Benowitz 1997].
Ten non-smoking patients with ulcerative colitis received nicotine tartrate
liquid enema at a dose of 3 mg nicotine base nightly for 1 week, then 6 mg for 3
weeks. Only 1 patient had a detectable peak nicotine concentration
(0.0023 mg/L) and none had a detectable trough concentration; the mean
trough plasma cotinine concentration was 0.012 mg/L [Sandborn et al. 1997].
A heavy smoker who abused lozenges containing nicotine (~240 lozenges of
0.4 mg nicotine each daily) had saliva and blood cotinine levels of 1.154 and
0.947 mg/L, respectively. At 20 min after his 70th 0.4 mg lozenge of the day, his
plasma nicotine concentration was 0.0321 mg/L [Foulds et al. 1998].
In 8 non-smoking subjects who consumed 8 lozenges of 1.1 mg nicotine,
mean nicotine levels increased from 0.0003–0.0064 mg/L [Foulds et al. 1998].
After 25 subjects were administered nicotine via transdermal patches (1
patch of 15 mg for 16 h coverage, or 2 different 21 mg 24 h patches; each patch
applied for 3 consecutive days), mean minimum and maximum plasma
nicotine concentrations of 0.00153 and 0.0123 mg/L were reported for the
15 mg patch, 0.013 and 0.0195 mg/L for the first 21 mg patch and 0.0119 and
0.0278 mg/L for the second 21 mg patch. The times taken to reach peak plasma
concentration was 6.0, 8.0, and 2.8 h, respectively, for the 3 patches [Fant et al.
2000].
Plasma nicotine levels in 5 healthy subjects given nicotine as infusions over
0.5–5 min were dose dependent: 11.5–14.1 mg/L and 19.02–26.3 mg/L with a
0.75 and 1.5 mg dose, respectively. They were generally highest with the
shortest infusion time at each dose. Oral fluid levels were highest at the
longest infusion time for each dose (19.1–49.1 mg/L and 26–104 mg/L with
the 0.75 and 1.5 mg doses, respectively) [Jenkins et al. 2005].
Average plasma and urine levels of nicotine in smokers were found to be
1263.1 mg/L and 1618 mg/L, respectively. Cotinine levels in plasma and urine
were 379.4 and 865 mg/L, respectively [Massadeh et al. 2009].
Toxicity Nicotine is highly toxic and, in acute poisoning, death may occur within a
few minutes because respiratory failure arises from paralysis of the respiratory
muscles. The lethal dose for an adult is between 40 and 60 mg. Blood concentrations
>5 mg/L may be fatal. The maximum permissible atmospheric concentration is
0.5 mg/m3.
In 5 adults who ingested 20–25 g nicotine and died within 1 h, postmortem
blood concentrations were between 11 and 63 mg/L (mean, 29) [Baselt, Cravey
1977].
Nine cases of self-poisoning associated with dermal exposure to 2–20
transdermal nicotine patches has been reported; all subjects recovered.
Plasma nicotine/cotinine levels did not correlate with severity of toxicity
[Woolf et al. 1996].
A report describes 36 exposures to transdermal nicotine in children aged
under 16 years; 18 children had dermal exposure, and the other 18 children
had bitten, chewed or swallowed part of a patch. Symptoms after dermal
exposure were associated with an estimated dose of at least 10 mg nicotine
[Woolf et al. 1997].
In 8 smokers who committed suicide, levels of nicotine and cotinine in
blood were 115 and 405 mg/L and in urine 1940 and 1170 mg/L, respectively.
Lower blood levels of nicotine and cotinine (33.2 and 140 mg/L, respectively)
and lower urine levels (246 and 179 mg/L, respectively) were found in 5
smokers who did not commit suicide [Moriya, Hashimoto 2004].
Another study also found higher levels of nicotine and cotinine in smokers
who committed suicide than in non-suicide smokers [Moriya et al. 2007].
High postmortem femoral muscle nicotine and cotinine levels of 213 and
488 mg/g, respectively, suggesting possible suicide, were found in an
adipocere body drowned ~5 months earlier [Nishimura et al. 2009].
Nicotine and cotinine femoral blood levels of 0.6 and 2 mg/L were found in
a subject who had cardiorespiratory failure induced by the additive effects of
tramadol and nicotine following self-poisoning [Solarino et al. 2010a].
In a fatal poisoning caused by nicotine (as ingested tobacco leaves) and
methomyl, nicotine levels in blood ranged from 222–733 mg/L. The stomach
contained 170 g of greenish liquid containing a small amount of shredded
tobacco leaves [Moriya, Hashimoto 2005].
Life-threatening nicotine intoxication is reported to occur after ingestion of
more than 6 cigarettes. However, a case of non-life-threatening toxicity
occurred in a 35-year-old man after ingestion of between 7 and 20 cigarettes
[Metzler et al. 2005].
A 42-year-old man who was found dead had high postmortem femoral
venous blood concentrations of nicotine and cotinine (2.2 mg/L) [Solarino
et al. 2010b].
A 27-year-old nurse survived after self-administering an IV injection of
5mL of cigarette soakage solution containing approximately 5.7 mg nicotine
[Hagiya et al. 2010].}

_{For other reports of suicide attempts with transdermal nicotine, see Engel,
Parmentier [1993], Montalto et al. [1994] and Labelle, Boulay [1999].
Bioavailability 30% (oral).
Half-life After inhalation or parenteral administration, plasma half-life, nicotine
0.5–2 h, cotinine 6–16 h (mean, 11).
Volume of Distribution 1–3 L/kg.
Clearance Plasma clearance, 10–30 mL/min/kg.
Protein Binding 5%.
Note For a review of the clinical pharmacokinetics of the nicotine inhaler,
see Schneider et al. [2001]; for a review of the pharmacology of nicotine and its
therapeutic use in smoking cessation and neurodegenerative disorders, see Balfour,
Fagerstrom [1996]; for a review of the clinical pharmacology of nicotine, see Zevin
et al. [1998]; for a review of the metabolism of nicotine, see Kyerematen, Vesell
[1991]; for a report of unintentional child poisonings from ingestion of conventional
and novel tobacco products, see Connolly et al. [2010].
Dose As an aid to smoking withdrawal, dose depends on the level of smoking and
formulation of preparation used.}

Это было давно, более 10 лет назад, детали уже стерлись. Общая фабула примерно такова: Последний раз некто видел умершего курящим в подъезде. Встал вопрос - это было непосредственно перед смертью? В крови и моче трупа никотин обнаружен не был, в моче присутствовал котинин. Время полувыведения (полужизни) в плазме для никотина - 0.5–2  ч, котинина 6–16 ч (среднее, 11 ч).

Думаю, что надлежащие выводы сделать не сложно.

 

 

А с точки зрения химии - никотин и его метаболиты, кофеин, гормоны - это своеобразные естественные внутренние стандарты, позволяющие с одной стороны удостовериться в аутентичности образца (в плане подмены), с другой - проконтролировать качество и погрешности всей цепочки от отбора аликвоты объекта и пробоподготовки до получения аналитического результата...

[Alexlp]

Естественно необходимо учитывать пределы обнаружения, достижимые в каждой конкретной лаборатории, которые зависят от оборудования, методов изолирования, аликвот образцов, квалификации экспертов...

Вопрос количественного определения зависит исключительно от наличия калибровочных стандартов никотина и котинина, и от востребованности этого количественного определения, а востребованность - от умения оценить результаты ...

[Dromedary]

В 18.04.2021 в 18:32, Alexlp сказал:

Никотин, и его основной метаболит - котинин, ...